VCV000259511.51 - ClinVar

NM_004655.4(AXIN2):c.148C>T (p.Pro50Ser)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign
Benign (14)

14 out of 18 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004655.4(AXIN2):c.148C>T (p.Pro50Ser)

Variation ID: 259511 Accession: VCV000259511.51

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q24.1 17: 65558473 (GRCh38) [ NCBI UCSC ] 17: 63554591 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 3, 2016	Feb 15, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_004655.4:c.148C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004646.3:p.Pro50Ser	missense
NM_001363813.1:c.148C>T	NP_001350742.1:p.Pro50Ser	missense
NC_000017.11:g.65558473G>A
NC_000017.10:g.63554591G>A
NG_012142.1:g.8150C>T
LRG_296:g.8150C>T
LRG_296t1:c.148C>T

... more HGVS ... less HGVS

Protein change

P50S

Other names

Canonical SPDI

NC_000017.11:65558472:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.33766 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.33635

Trans-Omics for Precision Medicine (TOPMed) 0.38490

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.39482

The Genome Aggregation Database (gnomAD) 0.39485

The Genome Aggregation Database (gnomAD), exomes 0.47417

The Genome Aggregation Database (gnomAD), exomes 0.50322

1000 Genomes Project 0.33766

The Genome Aggregation Database (gnomAD) 0.39067

Exome Aggregation Consortium (ExAC) 0.47373

Links

ClinGen: CA8719093 dbSNP: rs2240308 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
AXIN2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4355	4369

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (6)	criteria provided, multiple submitters, no conflicts	Mar 29, 2016	RCV000245378.24
not provided	Benign (4)	criteria provided, multiple submitters, no conflicts	Jul 30, 2025	RCV000586407.26
Oligodontia-cancer predisposition syndrome	Benign (5)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV000291911.28
Hereditary cancer-predisposing syndrome	Benign (3)	criteria provided, multiple submitters, no conflicts	Aug 25, 2025	RCV001011864.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Mar 03, 2015) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001855305.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: show This variant is associated with the following publications: (PMID: 26514524, 29114927, 28204848, 27153395, 16820935, 19065536) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000310589.1 First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 10, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV001172239.4 First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024	Comment: show This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jun 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Oligodontia-cancer predisposition syndrome	Myriad Genetics, Inc. Accession: SCV005082329.1 First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024	Comment: show This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal dominant inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005255563.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Jul 14, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Oligodontia-cancer predisposition syndrome	Genome-Nilou Lab Accession: SCV001775189.2 First in ClinVar: Aug 13, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 10, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary cancer-predisposing syndrome	GeneKor MSA Accession: SCV006311439.1 First in ClinVar: Aug 30, 2025 Last updated: Aug 30, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Oligodontia-cancer predisposition syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000929.8 First in ClinVar: Dec 17, 2019 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 29, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538387.1 First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016	Comment: show Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Method: Genome/Exome Filtration

Benign (Apr 26, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not provided	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000698514.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (1) PubMed: 16820935 Comment: show Variant summary: The c.148C>T variant affects a non-conserved nucleotide, resulting in amino acid change from Pro to Ser. 3/4 in-silico tools predict this variant to be benign. This variant is found in 56448/119156 control chromosomes (14394 homozygotes) from the large and broad populations of ExAC at a frequency of 0.4737319, which is about 3335 times greater than the maximal expected frequency of a pathogenic allele (0.0001421), suggesting this variant is a very common benign polymorphism. In a case-control study, authors found that the AXIN2 Pro50Ser SNP is associated with development of lung cancer as a protective SNP, while an association between the AXIN2 SNP and risk of colorectal cancer and of head and neck cancer was not observed (Kanzaki_IJMM_2006). Taken together, this variant was classified as Benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 07, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Oligodontia-cancer predisposition syndrome	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016246.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Aug 25, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary cancer-predisposing syndrome	Molecular Diagnostics Laboratory, Catalan Institute of Oncology Accession: SCV006324577.1 First in ClinVar: Sep 22, 2025 Last updated: Sep 22, 2025	Other databases https://spadahc.ciberisciii.es/v… https://spadahc.ciberisciii.es/variant/GRCH37/17%2063554591%20G/A Comment: show BA1 c.148C>T, located in exon 2 of theAXIN2 gene, is predicted to result in the substitution of Proline with Serine at codon 50, p.(Pro50Ser).The variant allele was found in 61109/116032 alleles, with a filtering allele frequency of 52.17% at 99% confidence, within the NFE population in the gnomAD v2.1.1 database (non-cancer data set) (BA1). Additional information has not been evaluated for this variant. Based on the currently available evidence, c.148C>T is classified as a benign variant according to ACMG guidelines. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 06, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Oligodontia-cancer predisposition syndrome	Illumina Laboratory Services, Illumina Accession: SCV000405754.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 30, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001472018.9 First in ClinVar: Jan 26, 2021 Last updated: Jan 24, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000691794.1 First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001743073.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Clinical Genetics, Academic Medical Center Study: VKGL Data-share Consensus Accession: SCV001919821.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV001928026.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Comment:

Variant summary: The c.148C>T variant affects a non-conserved nucleotide, resulting in amino acid change from Pro to Ser. 3/4 in-silico tools predict this variant to be benign. This variant is found in 56448/119156 control chromosomes (14394 homozygotes) from the large and broad populations of ExAC at a frequency of 0.4737319, which is about 3335 times greater than the maximal expected frequency of a pathogenic allele (0.0001421), suggesting this variant is a very common benign polymorphism. In a case-control study, authors found that the AXIN2 Pro50Ser SNP is associated with development of lung cancer as a protective SNP, while an association between the AXIN2 SNP and risk of colorectal cancer and of head and neck cancer was not observed (Kanzaki_IJMM_2006). Taken together, this variant was classified as Benign.

Comment:

BA1 c.148C>T, located in exon 2 of theAXIN2 gene, is predicted to result in the substitution of Proline with Serine at codon 50, p.(Pro50Ser).The variant allele was found in 61109/116032 alleles, with a filtering allele frequency of 52.17% at 99% confidence, within the NFE population in the gnomAD v2.1.1 database (non-cancer data set) (BA1). Additional information has not been evaluated for this variant. Based on the currently available evidence, c.148C>T is classified as a benign variant according to ACMG guidelines.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population.	Kanzaki H	International journal of molecular medicine	2006	PMID: 16820935
https://spadahc.ciberisciii.es/variant/GRCH37/17%2063554591%20G/A	-	-	-	-

Text-mined citations for rs2240308 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026