rs17036817

Variant summary

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

The NM_001406633.1(MSH2):​c.2897C>A​(p.Pro966His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 456,450 control chromosomes in the GnomAD database, including 965 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P966R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.035 ( 275 hom., cov: 32)
Exomes 𝑓: 0.041 ( 690 hom. )

Consequence

MSH2
NM_001406633.1 missense, splice_region

Scores

2

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.295
Variant links:
Genes affected

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSH2NM_001406633.1 linkuse as main transcriptc.2897C>A p.Pro966His missense_variant, splice_region_variant 18/19
MSH2NM_001406637.1 linkuse as main transcriptc.2753-29932C>A intron_variant
MSH2NR_176241.1 linkuse as main transcriptn.3099C>A splice_region_variant, non_coding_transcript_exon_variant 20/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt

Frequencies

GnomAD3 genomes
AF:
0.0354
AC:
5383
AN:
152030
Hom.:
274
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00645
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0510
Gnomad ASJ
AF:
0.0704
Gnomad EAS
AF:
0.303
Gnomad SAS
AF:
0.0427
Gnomad FIN
AF:
0.0439
Gnomad MID
AF:
0.0478
Gnomad NFE
AF:
0.0256
Gnomad OTH
AF:
0.0468
GnomAD3 exomes
AF:
0.0573
AC:
7707
AN:
134504
Hom.:
636
AF XY:
0.0543
AC XY:
3977
AN XY:
73250
show subpopulations
Gnomad AFR exome
AF:
0.00419
Gnomad AMR exome
AF:
0.0573
Gnomad ASJ exome
AF:
0.0606
Gnomad EAS exome
AF:
0.316
Gnomad SAS exome
AF:
0.0306
Gnomad FIN exome
AF:
0.0407
Gnomad NFE exome
AF:
0.0259
Gnomad OTH exome
AF:
0.0466
GnomAD4 exome
AF:
0.0409
AC:
12455
AN:
304302
Hom.:
690
Cov.:
0
AF XY:
0.0402
AC XY:
6968
AN XY:
173286
show subpopulations
Gnomad4 AFR exome
AF:
0.00464
Gnomad4 AMR exome
AF:
0.0559
Gnomad4 ASJ exome
AF:
0.0612
Gnomad4 EAS exome
AF:
0.314
Gnomad4 SAS exome
AF:
0.0321
Gnomad4 FIN exome
AF:
0.0421
Gnomad4 NFE exome
AF:
0.0260
Gnomad4 OTH exome
AF:
0.0443
GnomAD4 genome
AF:
0.0354
AC:
5383
AN:
152148
Hom.:
275
Cov.:
32
AF XY:
0.0381
AC XY:
2836
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00643
Gnomad4 AMR
AF:
0.0511
Gnomad4 ASJ
AF:
0.0704
Gnomad4 EAS
AF:
0.304
Gnomad4 SAS
AF:
0.0423
Gnomad4 FIN
AF:
0.0439
Gnomad4 NFE
AF:
0.0256
Gnomad4 OTH
AF:
0.0463
Alfa
AF:
0.0251
Hom.:
29
Bravo
AF:
0.0379

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.69
DANN
Benign
0.69

Splicing

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: rs17036817; hg19: chr2-47905390; API