Variant 2-31177766-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145122.2(CAPN14):c.1835A>G(p.His612Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000087 in 1,551,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CAPN14
NM_001145122.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.32

Variant links:

Genes affected

CAPN14 (HGNC:16664): (calpain 14) Calpains are a family of cytosolic calcium-activated cysteine proteases involved in a variety of cellular processes including apoptosis, cell division, modulation of integrin-cytoskeletal interactions, and synaptic plasticity (Dear et al., 2000 [PubMed 10964513]). CAPN14 belongs to the calpain large subunit family.[supplied by OMIM, Mar 2008]

CAPN14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006197214).

BP6

Variant 2-31177766-T-C is Benign according to our data. Variant chr2-31177766-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3137095.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN14	NM_001145122.2 linkuse as main transcript	c.1835A>G	p.His612Arg	missense_variant	19/22	ENST00000403897.4	NP_001138594.1	A8MX76-1B7Z467

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPN14	ENST00000403897.4 linkuse as main transcript	c.1835A>G	p.His612Arg	missense_variant	19/22	2	NM_001145122.2	ENSP00000385247.3	A8MX76-1
CAPN14	ENST00000398824.6 linkuse as main transcript	n.*1266A>G		non_coding_transcript_exon_variant	19/22	2		ENSP00000381805.2	F1LLU4
CAPN14	ENST00000398824.6 linkuse as main transcript	n.*1266A>G		3_prime_UTR_variant	19/22	2		ENSP00000381805.2	F1LLU4

Frequencies

GnomAD3 genomes

AF:

0.000466

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.000108

AC:

AN:

157674

Hom.:

AF XY:

0.0000600

AC XY:

AN XY:

83288

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1399612

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

690308

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000466

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000105

Hom.:

Bravo

AF:

0.000446

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000147

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0020

DANN

Benign

0.13

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00044

LIST_S2

Benign

0.32

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

3.7

REVEL

Benign

0.057

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MVP

0.014

ClinPred

0.016

GERP RS

-4.7

Varity_R

0.023

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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