chr2-47783024-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000652107.1(MSH6):​c.-37-7903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 460,784 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0061 ( 8 hom. )

Consequence

MSH6
ENST00000652107.1 intron

Scores

2

Clinical Significance

Benign reviewed by expert panel B:2

Conservation

PhyloP100: 0.890
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-47783024-C-T is Benign according to our data. Variant chr2-47783024-C-T is described in ClinVar as [Benign]. Clinvar id is 89160.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47783024-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00529 (804/151894) while in subpopulation AMR AF= 0.00944 (144/15258). AF 95% confidence interval is 0.00818. There are 3 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSH6ENST00000652107.1 linkuse as main transcriptc.-37-7903C>T intron_variant ENSP00000498629

Frequencies

GnomAD3 genomes
AF:
0.00528
AC:
801
AN:
151786
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00925
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00290
Gnomad FIN
AF:
0.00705
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00726
Gnomad OTH
AF:
0.00479
GnomAD4 exome
AF:
0.00610
AC:
1884
AN:
308890
Hom.:
8
AF XY:
0.00583
AC XY:
944
AN XY:
161918
show subpopulations
Gnomad4 AFR exome
AF:
0.00138
Gnomad4 AMR exome
AF:
0.0152
Gnomad4 ASJ exome
AF:
0.000775
Gnomad4 EAS exome
AF:
0.0000497
Gnomad4 SAS exome
AF:
0.00274
Gnomad4 FIN exome
AF:
0.00632
Gnomad4 NFE exome
AF:
0.00722
Gnomad4 OTH exome
AF:
0.00522
GnomAD4 genome
AF:
0.00529
AC:
804
AN:
151894
Hom.:
3
Cov.:
33
AF XY:
0.00505
AC XY:
375
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00157
Gnomad4 AMR
AF:
0.00944
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.00705
Gnomad4 NFE
AF:
0.00726
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00772
Hom.:
0
Bravo
AF:
0.00495
Asia WGS
AF:
0.00116
AC:
4
AN:
3452

ClinVar

Significance: Benign
Submissions summary: Benign:2
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% -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
11
DANN
Benign
0.92

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: rs181096360; hg19: chr2-48010163; API