rs13408008

Positions:

• chr2-47438558-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000251.3(MSH2):​c.1277-6990T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,250 control chromosomes in the GnomAD database, including 918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.098 (918 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: 0.505

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-47438558-T-G is Benign according to our data. Variant chr2-47438558-T-G is described in ClinVar as [Benign]. Clinvar id is 90608.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47438558-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1277-6990T>G		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1277-6990T>G		intron_variant		1	NM_000251.3	ENSP00000233146	P1

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14949 AN: 152132 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0982 AC: 14950 AN: 152250 Hom.: 918 Cov.: 32 AF XY: 0.0962 AC XY: 7161 AN XY: 74442

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.102

Alfa AF: 0.122 Hom.: 443

Bravo AF: 0.0910

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.81

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: rs13408008; hg19: chr2-47665697;