chr2-47408384-CT-C

Position:

• chr2-47408384-CT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000251.3(MSH2):​c.212-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 1,165,988 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.099 (0 hom.)
• Consequence: MSH2 NM_000251.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:7
• Conservation: PhyloP100: 1.95

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]

MSH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-47408384-CT-C is Benign according to our data. Variant chr2-47408384-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 183770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47408384-CT-C is described in Lovd as [Benign]. Variant chr2-47408384-CT-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.212-4delT		splice_region_variant, intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.212-4delT		splice_region_variant, intron_variant		1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 328 AN: 143830 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.00221

Gnomad SAS AF: 0.000442

Gnomad FIN AF: 0.00662

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00412

GnomAD4 exome AF: 0.0988 AC: 100934 AN: 1022094 Hom.: 0 Cov.: 0 AF XY: 0.0981 AC XY: 49956 AN XY: 509194

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0989

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0978

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.00229 AC: 329 AN: 143894 Hom.: 0 Cov.: 31 AF XY: 0.00251 AC XY: 175 AN XY: 69830

Gnomad4 AFR AF: 0.00307

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00119

Gnomad4 EAS AF: 0.00221

Gnomad4 SAS AF: 0.000442

Gnomad4 FIN AF: 0.00662

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.00409

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided Uncertain:1 Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -

Hereditary cancer-predisposing syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Feb 13, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Mar 01, 2018	Other strong data supporting benign classification -

Lynch syndrome 1 Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

May 13, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs746333570; hg19: chr2-47635523;