chr2-240603286-C-T

Variant names:

• chr2-240603286-C-T
• rs5030952
• ENST00000270364.11:c.274-13102C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000270364.11(CAPN10):​c.274-13102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,106 control chromosomes in the GnomAD database, including 5,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.20 (5150 hom., cov: 32)
• Consequence: CAPN10 ENST00000270364.11 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -3.36
• Publications: 47 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000270364.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	ENST00000270364.11	TSL:2	c.274-13102C>T		intron	N/A	ENSP00000270364.7
	CAPN10	ENST00000426297.1	TSL:3	n.*27-3101C>T		intron	N/A	ENSP00000404064.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30573 AN: 151988 Hom.: 5123 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 30643 AN: 152106 Hom.: 5150 Cov.: 32 AF XY: 0.203 AC XY: 15071 AN XY: 74398

African (AFR) AF: 0.451 AC: 18687 AN: 41462

American (AMR) AF: 0.200 AC: 3061 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1180 AN: 5142

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1491 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5135 AN: 67976

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.137 Hom.: 340

Bravo AF: 0.219

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus 1, susceptibility to Other:1

Oct 01, 2000

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.43
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5030952; hg19: chr2-241542703;