NM_000038.6(APC):c.7136C>G (p.Thr2379Ser) AND Familial adenomatous polyposis 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 26, 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:: RCV002527860.12

Allele description [Variation Report for NM_000038.6(APC):c.7136C>G (p.Thr2379Ser)]

NM_000038.6(APC):c.7136C>G (p.Thr2379Ser)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.7136C>G (p.Thr2379Ser)

HGVS:

NC_000005.10:g.112842730C>G
NG_008481.4:g.155210C>G
NM_000038.6:c.7136C>GMANE SELECT
NM_001127510.3:c.7136C>G
NM_001127511.3:c.7082C>G
NM_001354895.2:c.7136C>G
NM_001354896.2:c.7190C>G
NM_001354897.2:c.7166C>G
NM_001354898.2:c.7061C>G
NM_001354899.2:c.7052C>G
NM_001354900.2:c.7013C>G
NM_001354901.2:c.6959C>G
NM_001354902.2:c.6863C>G
NM_001354903.2:c.6833C>G
NM_001354904.2:c.6758C>G
NM_001354905.2:c.6656C>G
NM_001354906.2:c.6287C>G
NP_000029.2:p.Thr2379Ser
NP_001120982.1:p.Thr2379Ser
NP_001120983.2:p.Thr2361Ser
NP_001341824.1:p.Thr2379Ser
NP_001341825.1:p.Thr2397Ser
NP_001341826.1:p.Thr2389Ser
NP_001341827.1:p.Thr2354Ser
NP_001341828.1:p.Thr2351Ser
NP_001341829.1:p.Thr2338Ser
NP_001341830.1:p.Thr2320Ser
NP_001341831.1:p.Thr2288Ser
NP_001341832.1:p.Thr2278Ser
NP_001341833.1:p.Thr2253Ser
NP_001341834.1:p.Thr2219Ser
NP_001341835.1:p.Thr2096Ser
LRG_130:g.155210C>G
NC_000005.9:g.112178427C>G
NM_000038.5:c.7136C>G

Protein change:

T2096S

Links:

dbSNP: rs767691072

NCBI 1000 Genomes Browser:

rs767691072

Molecular consequence:

NM_000038.6:c.7136C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7136C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7082C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7136C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7166C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7061C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7052C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7013C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.6959C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.6863C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.6833C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.6758C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.6656C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6287C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Mus musculus YdjC homolog (bacterial) (Ydjc), transcript variant 1, mRNA
Mus musculus YdjC homolog (bacterial) (Ydjc), transcript variant 1, mRNA
gi|326693950|ref|NM_026940.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000647694	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004191606	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 26, 2024)	unknown	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

SCV000647694

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

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

SCV004191606

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 26, 2024)

unknown

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000647694.9

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

Description

This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2379 of the APC protein (p.Thr2379Ser). This variant is present in population databases (rs767691072, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 470078). 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 APC protein function with a negative predictive value of 95%. 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 Baylor Genetics, SCV004191606.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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