NM_004360.5(CDH1):c.164T>G (p.Val55Gly) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Oct 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000131233.7

Allele description [Variation Report for NM_004360.5(CDH1):c.164T>G (p.Val55Gly)]

NM_004360.5(CDH1):c.164T>G (p.Val55Gly)

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.164T>G (p.Val55Gly)
HGVS:
  • NC_000016.10:g.68801670T>G
  • NG_008021.1:g.69379T>G
  • NM_001317184.2:c.164T>G
  • NM_001317185.2:c.-1452T>G
  • NM_001317186.2:c.-1656T>G
  • NM_004360.5:c.164T>GMANE SELECT
  • NP_001304113.1:p.Val55Gly
  • NP_004351.1:p.Val55Gly
  • LRG_301t1:c.164T>G
  • LRG_301:g.69379T>G
  • NC_000016.9:g.68835573T>G
  • NM_004360.3:c.164T>G
  • NM_004360.4:c.164T>G
  • p.V55G
Protein change:
V55G
Links:
dbSNP: rs587778174
NCBI 1000 Genomes Browser:
rs587778174
Molecular consequence:
  • NM_001317185.2:c.-1452T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317186.2:c.-1656T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.164T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.164T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000186188Ambry Geneticscriteria provided, single submitter
Likely benign
(Oct 29, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000684372Color Health, Inccriteria provided, single submitter
Uncertain significance
(Oct 20, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]
PMID:
24728327
PMCID:
PMC3984285

Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer.

Wen H, Kim YC, Snyder C, Xiao F, Fleissner EA, Becirovic D, Luo J, Downs B, Sherman S, Cowan KH, Lynch HT, Wang SM.

BMC Cancer. 2014 Jun 26;14:470. doi: 10.1186/1471-2407-14-470.

PubMed [citation]
PMID:
24969172
PMCID:
PMC4083142
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000186188.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

Co-occurence with mutation in same gene (phase unknown);RNA Studies

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000684372.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This missense variant replaces valine with glycine at codon 55 of the CDH1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 24969172), an individual affected with cancer of the cecum (PMID: 28135145) who also has a pathogenic MUTYH covariant, and in unaffected individuals (PMID: 24728327; [FLOSSIES database](https://whi.color.com/variant/16-68835573-T-G)). This variant has been identified in 7/282786 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 19, 2021

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