rs330792

chr2-47781435-A-C

Variant summary

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

The ENST00000636749.1(U6):n.57A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,110 control chromosomes in the GnomAD database, including 799 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 0.089 (794 hom., cov: 32)
  • Exomes 𝑓: 0.56 (5 hom.)
• Consequence: U6 ENST00000636749.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

Genes affected

U6 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 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
U6	ENST00000636749.1	n.57A>C		non_coding_transcript_exon_variant	1/1
MSH6	ENST00000652107.1	c.-37-9492A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13495 AN: 151986 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 5 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0887 AC: 13498 AN: 152092 Hom.: 794 Cov.: 32 AF XY: 0.0904 AC XY: 6720 AN XY: 74328

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.116

Alfa AF: 0.115 Hom.: 1408

Bravo AF: 0.0794

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	8.4
Dann	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs330792; hg19: chr2-48008574;