VCV002430004.4 - ClinVar

NM_001007228.2(SPOP):c.216C>A (p.Asn72Lys)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Likely pathogenic (1); Uncertain significance (1)

2 out of 2 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_001007228.2(SPOP):c.216C>A (p.Asn72Lys)

Variation ID: 2430004 Accession: VCV002430004.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.33 17: 49619370 (GRCh38) [ NCBI UCSC ] 17: 47696732 (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	Feb 18, 2023	Feb 23, 2026	Feb 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001007228.2:c.216C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001007229.1:p.Asn72Lys	missense
NM_001007226.1:c.216C>A	NP_001007227.1:p.Asn72Lys	missense
NM_001007227.1:c.216C>A	NP_001007228.1:p.Asn72Lys	missense
NM_001007229.1:c.216C>A	NP_001007230.1:p.Asn72Lys	missense
NM_001007230.1:c.216C>A	NP_001007231.1:p.Asn72Lys	missense
NM_001370730.1:c.216C>A	NP_001357659.1:p.Asn72Lys	missense
NM_001370731.1:c.216C>A	NP_001357660.1:p.Asn72Lys	missense
NM_001370732.1:c.216C>A	NP_001357661.1:p.Asn72Lys	missense
NM_003563.3:c.216C>A	NP_003554.1:p.Asn72Lys	missense
NC_000017.11:g.49619370G>T
NC_000017.10:g.47696732G>T
NG_041815.1:g.63794C>A
LRG_1412:g.63794C>A
LRG_1412t1:c.216C>A	LRG_1412p1:p.Asn72Lys

... more HGVS ... less HGVS

Protein change

N72K

Other names

Canonical SPDI

NC_000017.11:49619369:G:T

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.

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

Links

ClinGen: CA400157118 dbSNP: rs544086490 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.
SPOP		-	-	GRCh38 GRCh37	243	255

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.
Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies	Likely pathogenic (1)	criteria provided, single submitter	Jul 26, 2022	RCV003127443.2
not provided	Uncertain significance (1)	criteria provided, single submitter	Feb 25, 2024	RCV005099268.2

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.
Likely pathogenic (Jul 26, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies	Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine Accession: SCV003804025.2 First in ClinVar: Feb 18, 2023 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: de novo Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: de novo Affected status: yes Sex: female

Uncertain significance (Feb 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005742841.2 First in ClinVar: Feb 25, 2025 Last updated: Feb 23, 2026	Comment: show This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 72 of the SPOP protein (p.Asn72Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPOP-related conditions. ClinVar contains an entry for this variant (Variation ID: 2430004). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPOP protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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

Comment:

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 72 of the SPOP protein (p.Asn72Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPOP-related conditions. ClinVar contains an entry for this variant (Variation ID: 2430004). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPOP protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs544086490 ...

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 Feb 25, 2026