NM_000038.6(APC):c.1902T>G (p.Ser634Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 9, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000222920.3

Allele description [Variation Report for NM_000038.6(APC):c.1902T>G (p.Ser634Arg)]

NM_000038.6(APC):c.1902T>G (p.Ser634Arg)

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.1902T>G (p.Ser634Arg)

HGVS:

NC_000005.10:g.112835109T>G
NG_008481.4:g.147589T>G
NM_000038.6:c.1902T>GMANE SELECT
NM_001127510.3:c.1902T>G
NM_001127511.3:c.1848T>G
NM_001354895.2:c.1902T>G
NM_001354896.2:c.1956T>G
NM_001354897.2:c.1932T>G
NM_001354898.2:c.1827T>G
NM_001354899.2:c.1818T>G
NM_001354900.2:c.1779T>G
NM_001354901.2:c.1725T>G
NM_001354902.2:c.1629T>G
NM_001354903.2:c.1599T>G
NM_001354904.2:c.1524T>G
NM_001354905.2:c.1422T>G
NM_001354906.2:c.1053T>G
NP_000029.2:p.Ser634Arg
NP_001120982.1:p.Ser634Arg
NP_001120983.2:p.Ser616Arg
NP_001341824.1:p.Ser634Arg
NP_001341825.1:p.Ser652Arg
NP_001341826.1:p.Ser644Arg
NP_001341827.1:p.Ser609Arg
NP_001341828.1:p.Ser606Arg
NP_001341829.1:p.Ser593Arg
NP_001341830.1:p.Ser575Arg
NP_001341831.1:p.Ser543Arg
NP_001341832.1:p.Ser533Arg
NP_001341833.1:p.Ser508Arg
NP_001341834.1:p.Ser474Arg
NP_001341835.1:p.Ser351Arg
LRG_130:g.147589T>G
NC_000005.9:g.112170806T>G
NM_000038.5:c.1902T>G

Protein change:

S351R

Links:

dbSNP: rs876659460

NCBI 1000 Genomes Browser:

rs876659460

Molecular consequence:

NM_000038.6:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.1848T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.1956T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.1932T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.1827T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.1818T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.1779T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.1725T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.1629T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.1599T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.1524T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.1422T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.1053T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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SRX1471767 (1)
SRA
tmtc2a [Onychostoma macrolepis]
tmtc2a [Onychostoma macrolepis]
Gene ID:131539566

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000275959	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 9, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24599579, 27696107 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000275959

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 9, 2024)

germline

clinical testing

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

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

Citations

PubMed

The UMD-APC database, a model of nation-wide knowledge base: update with data from 3,581 variations.

Grandval P, Blayau M, Buisine MP, Coulet F, Maugard C, Pinson S, Remenieras A, Tinat J, Uhrhammer N, Béroud C, Olschwang S.

Hum Mutat. 2014 May;35(5):532-6. doi: 10.1002/humu.22539. Epub 2014 Apr 7.

PubMed [citation]

PMID:: 24599579

Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

Rohlin A, Rambech E, Kvist A, Törngren T, Eiengård F, Lundstam U, Zagoras T, Gebre-Medhin S, Borg Å, Björk J, Nilbert M, Nordling M.

Fam Cancer. 2017 Apr;16(2):195-203. doi: 10.1007/s10689-016-9934-0.

PubMed [citation]

PMID:: 27696107
PMCID:: PMC5357488

Details of each submission

From Ambry Genetics, SCV000275959.7

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

Description

The c.1902T>G variant (also known as p.S634R), located in coding exon 14 of the APC gene, results from a T to G substitution at nucleotide position 1902. The serine at codon 634 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with APC-related disease (Ambry internal data; Grandval P et al. Hum. Mutat. 2014 May; 35(5):532-6; Rohlin A et al. Fam Cancer 2017 Apr;16(2):195-203.). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. This variant was reported to cause exon 14 skipping by mini-gene and RT-PCR RNA analysis (Grandval P et al. Hum. Mutat. 2014 May; 35(5):532-6). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Oct 13, 2024

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