NM_001903.5(CTNNA1):c.2512G>A (p.Val838Ile) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000804014.9

Allele description [Variation Report for NM_001903.5(CTNNA1):c.2512G>A (p.Val838Ile)]

NM_001903.5(CTNNA1):c.2512G>A (p.Val838Ile)

Gene:

CTNNA1:catenin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_001903.5(CTNNA1):c.2512G>A (p.Val838Ile)

Other names:

p.Val838Ile

HGVS:

NC_000005.10:g.138933880G>A
NG_047029.1:g.185485G>A
NM_001290307.3:c.*57G>A
NM_001290309.3:c.2203G>A
NM_001290310.3:c.2143G>A
NM_001290312.1:c.1402G>A
NM_001323982.2:c.2512G>A
NM_001323983.1:c.2512G>A
NM_001323984.2:c.2512G>A
NM_001323985.2:c.2485G>A
NM_001323986.2:c.2419G>A
NM_001323987.1:c.1402G>A
NM_001323988.1:c.1402G>A
NM_001323989.1:c.1402G>A
NM_001323990.1:c.1402G>A
NM_001323991.1:c.1402G>A
NM_001323992.1:c.1402G>A
NM_001323993.1:c.1402G>A
NM_001323994.1:c.1402G>A
NM_001323995.1:c.1402G>A
NM_001323996.1:c.1402G>A
NM_001323997.1:c.1402G>A
NM_001323998.1:c.1402G>A
NM_001323999.1:c.1402G>A
NM_001324000.1:c.1402G>A
NM_001324001.1:c.1267G>A
NM_001324002.1:c.*57G>A
NM_001324003.1:c.*57G>A
NM_001324004.1:c.*57G>A
NM_001324005.1:c.*57G>A
NM_001324006.1:c.1063G>A
NM_001324007.1:c.1063G>A
NM_001324008.1:c.1063G>A
NM_001324009.1:c.1063G>A
NM_001324010.1:c.1063G>A
NM_001324011.1:c.1309G>A
NM_001324012.1:c.1159G>A
NM_001324013.1:c.1159G>A
NM_001903.5:c.2512G>AMANE SELECT
NP_001277238.1:p.Val735Ile
NP_001277239.1:p.Val715Ile
NP_001277241.1:p.Val468Ile
NP_001310911.1:p.Val838Ile
NP_001310912.1:p.Val838Ile
NP_001310913.1:p.Val838Ile
NP_001310914.1:p.Val829Ile
NP_001310915.1:p.Val807Ile
NP_001310916.1:p.Val468Ile
NP_001310917.1:p.Val468Ile
NP_001310918.1:p.Val468Ile
NP_001310919.1:p.Val468Ile
NP_001310920.1:p.Val468Ile
NP_001310921.1:p.Val468Ile
NP_001310922.1:p.Val468Ile
NP_001310923.1:p.Val468Ile
NP_001310924.1:p.Val468Ile
NP_001310925.1:p.Val468Ile
NP_001310926.1:p.Val468Ile
NP_001310927.1:p.Val468Ile
NP_001310928.1:p.Val468Ile
NP_001310929.1:p.Val468Ile
NP_001310930.1:p.Val423Ile
NP_001310935.1:p.Val355Ile
NP_001310936.1:p.Val355Ile
NP_001310937.1:p.Val355Ile
NP_001310938.1:p.Val355Ile
NP_001310939.1:p.Val355Ile
NP_001310940.1:p.Val437Ile
NP_001310941.1:p.Val387Ile
NP_001310942.1:p.Val387Ile
NP_001894.2:p.Val838Ile
NC_000005.9:g.138269569G>A
NM_001903.2:c.2512G>A
NM_001903.3:c.2512G>A

Protein change:

V355I

Links:

dbSNP: rs1054245968

NCBI 1000 Genomes Browser:

rs1054245968

Molecular consequence:

NM_001290307.3:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001324002.1:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001324003.1:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001324004.1:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001324005.1:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001290309.3:c.2203G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001290310.3:c.2143G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001290312.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323982.2:c.2512G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323983.1:c.2512G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323984.2:c.2512G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323985.2:c.2485G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323986.2:c.2419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323987.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323988.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323989.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323990.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323991.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323992.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323993.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323994.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323995.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323996.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323997.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323998.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323999.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324000.1:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324001.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324006.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324007.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324008.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324009.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324010.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324011.1:c.1309G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324012.1:c.1159G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324013.1:c.1159G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001903.5:c.2512G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000943904	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32051609, 28492532
SCV005411873	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 4, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000943904

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005411873

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 4, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer.

Clark DF, Michalski ST, Tondon R, Nehoray B, Ebrahimzadeh J, Hughes SK, Soper ER, Domchek SM, Rustgi AK, Pineda-Alvarez D, Anderson MJ, Katona BW.

Genet Med. 2020 May;22(5):840-846. doi: 10.1038/s41436-020-0753-1. Epub 2020 Feb 13.

PubMed [citation]

PMID:: 32051609
PMCID:: PMC7200596

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000943904.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 838 of the CTNNA1 protein (p.Val838Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with breast and/or gastric cancer (PMID: 32051609). ClinVar contains an entry for this variant (Variation ID: 649148). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV005411873.1

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

Description

BP4, PP2, PM2_moderate

#	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		1	not provided	not provided	not provided

Last Updated: Nov 30, 2024

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