Variant chr2-240592062-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_023083.4(CAPN10):c.600A>G(p.Pro200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,608,754 control chromosomes in the GnomAD database, including 21,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1450 hom., cov: 34)

Exomes 𝑓: 0.16 ( 19908 hom. )

Consequence

CAPN10
NM_023083.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.53

Variant links:

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

CAPN10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-240592062-A-G is Benign according to our data. Variant chr2-240592062-A-G is described in ClinVar as [Benign]. Clinvar id is 3056633.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN10	NM_023083.4 linkuse as main transcript	c.600A>G	p.Pro200=	synonymous_variant	4/12	ENST00000391984.7	NP_075571.2
CAPN10	NM_023085.4 linkuse as main transcript	c.600A>G	p.Pro200=	synonymous_variant	4/10		NP_075573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7 linkuse as main transcript	c.600A>G	p.Pro200=	synonymous_variant	4/12	1	NM_023083.4	ENSP00000375844	P1	Q9HC96-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19133

AN:

152170

Hom.:

1449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0992

Gnomad ASJ

AF:

0.0835

Gnomad EAS

AF:

0.0983

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.147

AC:

34872

AN:

237336

Hom.:

2848

AF XY:

0.153

AC XY:

19685

AN XY:

128790

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.0834

Gnomad ASJ exome

AF:

0.0904

Gnomad EAS exome

AF:

0.0986

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.162

AC:

235490

AN:

1456466

Hom.:

19908

Cov.:

AF XY:

0.162

AC XY:

117566

AN XY:

724172

show subpopulations

Gnomad4 AFR exome

AF:

0.0416

Gnomad4 AMR exome

AF:

0.0839

Gnomad4 ASJ exome

AF:

0.0898

Gnomad4 EAS exome

AF:

0.0909

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.126

AC:

19143

AN:

152288

Hom.:

1450

Cov.:

AF XY:

0.127

AC XY:

9449

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.0992

Gnomad4 ASJ

AF:

0.0835

Gnomad4 EAS

AF:

0.0986

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.152

Hom.:

2439

Bravo

AF:

0.114

Asia WGS

AF:

0.147

AC:

512

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CAPN10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.28

DANN

Benign

0.23

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