2-47783024-C-T

Position:

• chr2-47783024-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: 0.890

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]

ACMG classification

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
MSH6	ENST00000652107.1	c.-37-7903C>T		intron_variant				ENSP00000498629

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 801 AN: 151786 Hom.: 3 Cov.: 33

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

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

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

Submissions by phenotype

Lynch syndrome Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough 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

Other links and lift over

dbSNP: rs181096360; hg19: chr2-48010163;