2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Position:

• chr2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The ENST00000233146.7(MSH2):​c.942+3_942+9delAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00489 in 1,039,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (0 hom.)
• Consequence: MSH2 ENST00000233146.7 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.75

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 2-47414420-TAAAAAAA-T is Benign according to our data. Variant chr2-47414420-TAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1685774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414420-TAAAAAAA-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00519 (5072/977500) while in subpopulation EAS AF= 0.0105 (246/23474). AF 95% confidence interval is 0.00941. There are 0 homozygotes in gnomad4_exome. There are 2549 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.942+23_942+29delAAAAAAA		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.942+3_942+9delAAAAAAA		splice_region_variant, intron_variant		1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 10 AN: 62234 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000217

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00519 AC: 5072 AN: 977500 Hom.: 0 AF XY: 0.00525 AC XY: 2549 AN XY: 485632

Gnomad4 AFR exome AF: 0.00614

Gnomad4 AMR exome AF: 0.00825

Gnomad4 ASJ exome AF: 0.00709

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.00359

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.00683

GnomAD4 genome AF: 0.000161 AC: 10 AN: 62234 Hom.: 0 Cov.: 0 AF XY: 0.0000726 AC XY: 2 AN XY: 27562

Gnomad4 AFR AF: 0.000103

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00158

Gnomad4 NFE AF: 0.000217

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -

Hereditary cancer-predisposing syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	Feb 22, 2023	- -
Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Apr 06, 2021	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11309117; hg19: chr2-47641559;