2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000233146.7(MSH2):c.942+2_942+3insAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). The gene MSH2 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

MSH2
ENST00000233146.7 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.32

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Lynch syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen
Lynch syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Muir-Torre syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp
mismatch repair cancer syndrome 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
mismatch repair cancer syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
ovarian cancer
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
malignant pancreatic neoplasm
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
rhabdomyosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MSH2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000233146.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for MSH2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 2-47414420-T-TAAAAAA is Benign according to our data. Variant chr2-47414420-T-TAAAAAA is described in ClinVar as Benign. ClinVar VariationId is 1685754.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000233146.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSH2	NM_000251.3	MANE Select	c.942+24_942+29dupAAAAAA	intron	N/A	NP_000242.1	P43246-1
MSH2	NM_001406674.1		c.942+24_942+29dupAAAAAA	intron	N/A	NP_001393603.1
MSH2	NM_001406631.1		c.942+24_942+29dupAAAAAA	intron	N/A	NP_001393560.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSH2	ENST00000233146.7	TSL:1 MANE Select	c.942+2_942+3insAAAAAA	splice_region intron	N/A	ENSP00000233146.2	P43246-1
MSH2	ENST00000406134.5	TSL:1	c.942+2_942+3insAAAAAA	splice_region intron	N/A	ENSP00000384199.1	E9PHA6
MSH2	ENST00000918107.1		c.993+2_993+3insAAAAAA	splice_region intron	N/A	ENSP00000588166.1

Frequencies

GnomAD3 genomes

AF:

0.0000161

AC:

AN:

62234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000305

AC:

AN:

982176

Hom.:

Cov.:

AF XY:

0.00000615

AC XY:

AN XY:

488170

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

21594

American (AMR)

AF:

0.00

AC:

AN:

18678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14772

East Asian (EAS)

AF:

0.00

AC:

AN:

23652

South Asian (SAS)

AF:

0.0000174

AC:

AN:

57452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2506

European-Non Finnish (NFE)

AF:

0.00000128

AC:

AN:

783506

Other (OTH)

AF:

0.0000259

AC:

AN:

38558

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00250614), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000161

AC:

AN:

62234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27562

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000516

AC:

AN:

19366

American (AMR)

AF:

0.00

AC:

AN:

4136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1768

East Asian (EAS)

AF:

0.00

AC:

AN:

1634

South Asian (SAS)

AF:

0.00

AC:

AN:

1108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

32198

Other (OTH)

AF:

0.00

AC:

AN:

778

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over