Variant chr2-47462117-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000251.3(MSH2):c.1387-914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 149,164 control chromosomes in the GnomAD database, including 24,128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 24128 hom., cov: 25)

Consequence

MSH2
NM_000251.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.875

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3 link	c.1387-914A>G		intron_variant		ENST00000233146.7	NP_000242.1	P43246-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 link	c.1387-914A>G		intron_variant		1	NM_000251.3	ENSP00000233146.2		P43246-1

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

81096

AN:

149038

Hom.:

24082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.426

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.505

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

GnomAD4 genome

AF:

0.544

AC:

81202

AN:

149164

Hom.:

24128

Cov.:

AF XY:

0.545

AC XY:

39610

AN XY:

72618

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.499

Hom.:

2534

Bravo

AF:

0.545

Asia WGS

AF:

0.581

AC:

2014

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.2

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over