NM_004360.5(CDH1):c.2512A>G (p.Ser838Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Sep 25, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000115857.21

Allele description [Variation Report for NM_004360.5(CDH1):c.2512A>G (p.Ser838Gly)]

NM_004360.5(CDH1):c.2512A>G (p.Ser838Gly)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2512A>G (p.Ser838Gly)

Other names:

p.S838G:AGC>GGC

HGVS:

NC_000016.10:g.68833362A>G
NG_008021.1:g.101071A>G
NM_001317184.2:c.2329A>G
NM_001317185.2:c.964A>G
NM_001317186.2:c.547A>G
NM_004360.5:c.2512A>GMANE SELECT
NP_001304113.1:p.Ser777Gly
NP_001304114.1:p.Ser322Gly
NP_001304115.1:p.Ser183Gly
NP_004351.1:p.Ser838Gly
LRG_301t1:c.2512A>G
LRG_301:g.101071A>G
NC_000016.9:g.68867265A>G
NM_004360.3:c.2512A>G
NM_004360.4:c.2512A>G
P12830:p.Ser838Gly
p.S838G
NM_004360.4(CDH1):c.2512A>G

Protein change:

S183G; SER838GLY

Links:

UniProtKB: P12830#VAR_001322; OMIM: 192090.0003; dbSNP: rs121964872

Molecular consequence:

NM_001317184.2:c.2329A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.964A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317186.2:c.547A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.2512A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000183966	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Nov 9, 2018)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 19139070, 22470475, 25186627, 27616075, 27930734, 28767289, 28993866, 30311375, 30374176, 31159747 Citation Link,
SCV000821975	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000910736	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002529144	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Oct 12, 2020)	germline	curation	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases.

Ryu GM, Song P, Kim KW, Oh KS, Park KJ, Kim JH.

Nucleic Acids Res. 2009 Mar;37(4):1297-307. doi: 10.1093/nar/gkn1008. Epub 2009 Jan 12.

PubMed [citation]

PMID:: 19139070
PMCID:: PMC2651802

E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer.

Simões-Correia J, Figueiredo J, Lopes R, Stricher F, Oliveira C, Serrano L, Seruca R.

PLoS One. 2012;7(3):e33783. doi: 10.1371/journal.pone.0033783. Epub 2012 Mar 21.

PubMed [citation]

PMID:: 22470475
PMCID:: PMC3309996

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000183966.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This alteration is classified as likely 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneKor MSA, SCV000821975.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000910736.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002529144.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 20, 2026

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