rs3136228

Variant names:

• chr2-47782677-T-G
• rs3136228
• ENST00000652107.1:c.-37-8250T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: 0.0530

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH6	ENST00000652107.1	c.-37-8250T>G		intron_variant	Intron 3 of 11			ENSP00000498629.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44313 AN: 152070 Hom.: 7057 Cov.: 33

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

Gnomad4 AFR AF: 0.243 AC: 0.242969 AN: 0.242969

Gnomad4 AMR AF: 0.230 AC: 0.229578 AN: 0.229578

Gnomad4 ASJ AF: 0.267 AC: 0.266705 AN: 0.266705

Gnomad4 EAS AF: 0.00407 AC: 0.00407135 AN: 0.00407135

Gnomad4 SAS AF: 0.132 AC: 0.131841 AN: 0.131841

Gnomad4 FIN AF: 0.323 AC: 0.322669 AN: 0.322669

Gnomad4 NFE AF: 0.365 AC: 0.364554 AN: 0.364554

Gnomad4 OTH AF: 0.306 AC: 0.306238 AN: 0.306238

Alfa AF: 0.336 Hom.: 32044

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

Submissions by phenotype

Lynch syndrome Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >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

Other links and lift over

dbSNP: rs3136228; hg19: chr2-48009816;