chr2-47462117-A-G

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

2

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]

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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
MSH2NM_000251.3 linkc.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
MSH2ENST00000233146.7 linkc.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.:
25
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.:
25
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.

Other links and lift over

dbSNP: rs6711675; hg19: chr2-47689256; API