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NC_000015.9:g.(?_32988695)_(33004759_?)dup AND Familial colorectal cancer

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 6, 2019
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:
RCV000653702.11

Allele description [Variation Report for NC_000015.9:g.(?_32988695)_(33004759_?)dup]

NC_000015.9:g.(?_32988695)_(33004759_?)dup

Genes:
GREM1:gremlin 1, DAN family BMP antagonist [Gene - OMIM - HGNC]
ARHGAP11A-SCG5:ARHGAP11A-SCG5 readthrough [Gene - HGNC]
LOC125078054:Sharpr-MPRA regulatory region 2498 [Gene]
SCG5:secretogranin V [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
15q13.3
Genomic location:
Preferred name:
NC_000015.9:g.(?_32988695)_(33004759_?)dup
HGVS:
NC_000015.9:g.(?_32988695)_(33004759_?)dup

Condition(s)

Name:
Familial colorectal cancer
Identifiers:
MONDO: MONDO:0023113; MedGen: CN280943

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000775585Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 6, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1.

Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, Davis H, Kaur K, Heinimann K, Howarth K; HMPS Collaboration., East J, Taylor J, Thomas H, Tomlinson I.

Nat Genet. 2012 May 6;44(6):699-703. doi: 10.1038/ng.2263.

PubMed [citation]
PMID:
22561515
PMCID:
PMC4594751

GREM1 germline mutation screening in Ashkenazi Jewish patients with familial colorectal cancer.

Laitman Y, Jaeger E, Katz L, Tomlinson I, Friedman E.

Genet Res (Camb). 2015 May 20;97:e11. doi: 10.1017/S0016672315000105.

PubMed [citation]
PMID:
25992589
PMCID:
PMC4745135
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000775585.7

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

Description

This variant results in a copy number gain of the genomic region encompassing the promoter of the GREM1 gene. The precise boundaries of this event are unknown. Two different tandem duplications (40 kb and 16 kb) spanning the 3' end of the SCG5 gene and the region upstream of the GREM1 gene have been reported in families with hereditary mixed polyposis syndrome (PMID: 22561515, 25992589, 26493165). However, the variant identified in this individual occurs further upstream of those variants, and the impact of the this duplicated sequence on GREM1 expression and function has not been established. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of this non-coding change is currently unknown. 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.

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

Last Updated: Sep 29, 2024