2-47755433-G-A

Position:

• chr2-47755433-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652107.1(MSH6):​c.-38+17927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,826 control chromosomes in the GnomAD database, including 14,725 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 0.43 (14725 hom., cov: 30)
• Consequence: MSH6 ENST00000652107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

LOC105374589 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374589	XR_940070.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH6	ENST00000652107.1	c.-38+17927G>A		intron_variant				ENSP00000498629
MSH6	ENST00000454137.5	n.621-2256G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65429 AN: 151710 Hom.: 14689 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65511 AN: 151826 Hom.: 14725 Cov.: 30 AF XY: 0.440 AC XY: 32621 AN XY: 74208

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.426

Alfa AF: 0.388 Hom.: 15358

Bravo AF: 0.441

Asia WGS AF: 0.634 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs441327; hg19: chr2-47982572;