NM_000038.6(APC):c.1892_1904delinsAAT (p.Ile631fs) AND Familial multiple polyposis syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jun 24, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001192828.1

Allele description [Variation Report for NM_000038.6(APC):c.1892_1904delinsAAT (p.Ile631fs)]

NM_000038.6(APC):c.1892_1904delinsAAT (p.Ile631fs)

Gene:
APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
5q22.2
Genomic location:
Preferred name:
NM_000038.6(APC):c.1892_1904delinsAAT (p.Ile631fs)
HGVS:
  • NC_000005.10:g.112835099_112835111delinsAAT
  • NG_008481.4:g.147579_147591delinsAAT
  • NM_000038.6:c.1892_1904delinsAATMANE SELECT
  • NM_001127510.3:c.1892_1904delinsAAT
  • NM_001127511.3:c.1838_1850delinsAAT
  • NM_001354895.2:c.1892_1904delinsAAT
  • NM_001354896.2:c.1946_1958delinsAAT
  • NM_001354897.2:c.1922_1934delinsAAT
  • NM_001354898.2:c.1817_1829delinsAAT
  • NM_001354899.2:c.1808_1820delinsAAT
  • NM_001354900.2:c.1769_1781delinsAAT
  • NM_001354901.2:c.1715_1727delinsAAT
  • NM_001354902.2:c.1619_1631delinsAAT
  • NM_001354903.2:c.1589_1601delinsAAT
  • NM_001354904.2:c.1514_1526delinsAAT
  • NM_001354905.2:c.1412_1424delinsAAT
  • NM_001354906.2:c.1043_1055delinsAAT
  • NP_000029.2:p.Ile631fs
  • NP_001120982.1:p.Ile631fs
  • NP_001120983.2:p.Ile613fs
  • NP_001341824.1:p.Ile631fs
  • NP_001341825.1:p.Ile649fs
  • NP_001341826.1:p.Ile641fs
  • NP_001341827.1:p.Ile606fs
  • NP_001341828.1:p.Ile603fs
  • NP_001341829.1:p.Ile590fs
  • NP_001341830.1:p.Ile572fs
  • NP_001341831.1:p.Ile540fs
  • NP_001341832.1:p.Ile530fs
  • NP_001341833.1:p.Ile505fs
  • NP_001341834.1:p.Ile471fs
  • NP_001341835.1:p.Ile348fs
  • LRG_130:g.147579_147591delinsAAT
  • NC_000005.9:g.112170796_112170808delinsAAT
  • NM_000038.5:c.1892_1904delTTATTGAAAGTGGinsAAT
  • NM_000038.5:c.1892_1904delinsAAT
Protein change:
I348fs
Links:
dbSNP: rs863225319
NCBI 1000 Genomes Browser:
rs863225319
Molecular consequence:
  • NM_000038.6:c.1892_1904delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127510.3:c.1892_1904delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127511.3:c.1838_1850delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354895.2:c.1892_1904delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354896.2:c.1946_1958delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354897.2:c.1922_1934delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354898.2:c.1817_1829delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354899.2:c.1808_1820delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354900.2:c.1769_1781delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354901.2:c.1715_1727delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354902.2:c.1619_1631delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354903.2:c.1589_1601delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354904.2:c.1514_1526delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354905.2:c.1412_1424delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354906.2:c.1043_1055delinsAAT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Familial multiple polyposis syndrome (FAP)
Synonyms:
Adenomatous polyposis coli; Familial adenomatous polyposis of the colon; Familial polyposis of the colon; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0021055; MedGen: C0032580; OMIM: PS175100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001361207Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jun 24, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361207.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: APC c.1892_1904delinsAAT (p.Ile631LysfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.2547_2550delTAGA, p.Asp849fsX11; c.3183_3187delACAAA, p.Gln1062fsX1; c.3927_3931delAAAGA, p.Glu1309fsX4). The variant was absent in 251346 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1892_1904delinsAAT in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Oct 8, 2021

Support Center