chr2-47783515-C-G

Position:

chr2-47783515-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000179.3(MSH6):c.260+22C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,391,608 control chromosomes in the GnomAD database, including 21,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.13 ( 1551 hom., cov: 30)

Exomes 𝑓: 0.17 ( 20096 hom. )

Consequence

MSH6
NM_000179.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:10

Conservation

PhyloP100: -2.21

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]

MSH6 links:

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=-0.75).

BP6

Variant 2-47783515-C-G is Benign according to our data. Variant chr2-47783515-C-G is described in ClinVar as [Benign]. Clinvar id is 89295.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47783515-C-G is described in Lovd as [Benign]. Variant chr2-47783515-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH6	NM_000179.3 linkuse as main transcript	c.260+22C>G		intron_variant		ENST00000234420.11	NP_000170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH6	ENST00000234420.11 linkuse as main transcript	c.260+22C>G		intron_variant		1	NM_000179.3	ENSP00000234420	P4	P52701-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19187

AN:

148068

Hom.:

1553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.00103

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.139

AC:

4248

AN:

30570

Hom.:

373

AF XY:

0.142

AC XY:

2216

AN XY:

15592

show subpopulations

Gnomad AFR exome

AF:

0.0588

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0793

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.175

AC:

217153

AN:

1243430

Hom.:

20096

Cov.:

AF XY:

0.173

AC XY:

103601

AN XY:

600298

show subpopulations

Gnomad4 AFR exome

AF:

0.0432

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0785

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.129

AC:

19185

AN:

148178

Hom.:

1551

Cov.:

AF XY:

0.126

AC XY:

9088

AN XY:

72358

show subpopulations

Gnomad4 AFR

AF:

0.0552

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.00104

Gnomad4 SAS

AF:

0.0614

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.140

Hom.:

227

Bravo

AF:

0.127

Asia WGS

AF:

0.0410

AC:

146

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:10

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 02, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided

Uncertain:1Benign:2

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lynch syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Lynch syndrome

Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Jul 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.6

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over