2-47476888-G-C

Variant names:

• chr2-47476888-G-C
• rs4638843
• NM_000251.3:c.2210+317G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000251.3(MSH2):​c.2210+317G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,236 control chromosomes in the GnomAD database, including 64,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.92 (64709 hom., cov: 31)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: -0.0920

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-47476888-G-C is Benign according to our data. Variant chr2-47476888-G-C is described in ClinVar as [Benign]. Clinvar id is 90924.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47476888-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.2210+317G>C		intron_variant	Intron 13 of 15	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.2210+317G>C		intron_variant	Intron 13 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140070 AN: 152118 Hom.: 64648 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.914

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.921 AC: 140190 AN: 152236 Hom.: 64709 Cov.: 31 AF XY: 0.924 AC XY: 68781 AN XY: 74428

African (AFR) AF: 0.977 AC: 40590 AN: 41556

American (AMR) AF: 0.916 AC: 14008 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3093 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.976 AC: 4710 AN: 4824

European-Finnish (FIN) AF: 0.923 AC: 9773 AN: 10592

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59810 AN: 68004

Other (OTH) AF: 0.915 AC: 1934 AN: 2114

Alfa AF: 0.884 Hom.: 2907

Bravo AF: 0.924

Asia WGS AF: 0.986 AC: 3430 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.82
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4638843; hg19: chr2-47704027;