rs3136228

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000652107.1(MSH6):​c.-37-8250T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,188 control chromosomes in the GnomAD database, including 7,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.29 ( 7066 hom., cov: 33)

Consequence

MSH6
ENST00000652107.1 intron

Scores

2

Clinical Significance

Benign reviewed by expert panel B:1

Conservation

PhyloP100: 0.0530
Variant links:
Genes affected
MSH6 (HGNC:7329): (mutS homolog 6) This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 2-47782677-T-G is Benign according to our data. Variant chr2-47782677-T-G is described in ClinVar as [Benign]. Clinvar id is 89163.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47782677-T-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSH6ENST00000652107.1 linkuse as main transcriptc.-37-8250T>G intron_variant

Frequencies

GnomAD3 genomes
AF:
0.291
AC:
44313
AN:
152070
Hom.:
7057
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.243
Gnomad AMI
AF:
0.254
Gnomad AMR
AF:
0.230
Gnomad ASJ
AF:
0.267
Gnomad EAS
AF:
0.00406
Gnomad SAS
AF:
0.131
Gnomad FIN
AF:
0.323
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.365
Gnomad OTH
AF:
0.311
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.291
AC:
44339
AN:
152188
Hom.:
7066
Cov.:
33
AF XY:
0.284
AC XY:
21130
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.243
Gnomad4 AMR
AF:
0.230
Gnomad4 ASJ
AF:
0.267
Gnomad4 EAS
AF:
0.00407
Gnomad4 SAS
AF:
0.132
Gnomad4 FIN
AF:
0.323
Gnomad4 NFE
AF:
0.365
Gnomad4 OTH
AF:
0.306
Alfa
AF:
0.352
Hom.:
12289
Bravo
AF:
0.284
Asia WGS
AF:
0.0910
AC:
319
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Lynch syndrome Benign:1
Benign, reviewed by expert panelresearchInternational Society for Gastrointestinal Hereditary Tumours (InSiGHT)Sep 05, 2013MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.3
DANN
Benign
0.44

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: rs3136228; hg19: chr2-48009816; API