Variant chr2-47466898-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000251.3(MSH2):c.1661+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,402,120 control chromosomes in the GnomAD database, including 1,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.031 ( 102 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1222 hom. )

Consequence

MSH2
NM_000251.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2 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=-0.83).

BP6

Variant 2-47466898-T-C is Benign according to our data. Variant chr2-47466898-T-C is described in ClinVar as [Benign]. Clinvar id is 90723.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47466898-T-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3 linkuse as main transcript	c.1661+90T>C		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 linkuse as main transcript	c.1661+90T>C		intron_variant		1	NM_000251.3	ENSP00000233146	P1	P43246-1

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4751

AN:

152236

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00854

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0430

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0449

GnomAD4 exome

AF:

0.0394

AC:

49184

AN:

1249766

Hom.:

1222

AF XY:

0.0392

AC XY:

24761

AN XY:

631820

show subpopulations

Gnomad4 AFR exome

AF:

0.00731

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.0847

Gnomad4 EAS exome

AF:

0.000131

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0432

GnomAD4 genome

AF:

0.0312

AC:

4747

AN:

152354

Hom.:

102

Cov.:

AF XY:

0.0293

AC XY:

2180

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00851

Gnomad4 AMR

AF:

0.0429

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0458

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0414

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

research

Mayo Clinic Laboratories, Mayo Clinic

- -

Lynch syndrome

Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.3

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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