chr2-240591700-A-C

Variant names:

• chr2-240591700-A-C
• rs41266971
• NM_023083.4:c.471-233A>C

Variant summary

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

The NM_023083.4(CAPN10):​c.471-233A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 567,468 control chromosomes in the GnomAD database, including 1,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.089 (691 hom., cov: 34)
  • Exomes 𝑓: 0.069 (1165 hom.)
• Consequence: CAPN10 NM_023083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023083.4. 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
	CAPN10	NM_023083.4	MANE Select	c.471-233A>C		intron	N/A	NP_075571.2
	CAPN10	NM_023085.4		c.471-233A>C		intron	N/A	NP_075573.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.471-233A>C		intron	N/A	ENSP00000375844.2
	CAPN10	ENST00000354082.8	TSL:1	c.471-233A>C		intron	N/A	ENSP00000270362.6
	CAPN10	ENST00000352879.8	TSL:1	c.141+4648A>C		intron	N/A	ENSP00000289381.6

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13529 AN: 152176 Hom.: 688 Cov.: 34

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0691 AC: 28671 AN: 415174 Hom.: 1165 Cov.: 3 AF XY: 0.0685 AC XY: 14781 AN XY: 215638

African (AFR) AF: 0.136 AC: 1623 AN: 11958

American (AMR) AF: 0.0393 AC: 655 AN: 16654

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 1078 AN: 13228

East Asian (EAS) AF: 0.0194 AC: 577 AN: 29692

South Asian (SAS) AF: 0.0579 AC: 2163 AN: 37354

European-Finnish (FIN) AF: 0.0989 AC: 2804 AN: 28362

Middle Eastern (MID) AF: 0.0786 AC: 149 AN: 1896

European-Non Finnish (NFE) AF: 0.0710 AC: 17838 AN: 251390

Other (OTH) AF: 0.0724 AC: 1784 AN: 24640

GnomAD4 genome AF: 0.0889 AC: 13543 AN: 152294 Hom.: 691 Cov.: 34 AF XY: 0.0894 AC XY: 6659 AN XY: 74464

African (AFR) AF: 0.139 AC: 5764 AN: 41560

American (AMR) AF: 0.0471 AC: 721 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3472

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5182

South Asian (SAS) AF: 0.0548 AC: 265 AN: 4834

European-Finnish (FIN) AF: 0.110 AC: 1166 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4979 AN: 68024

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0354 Hom.: 31

Bravo AF: 0.0864

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41266971; hg19: chr2-241531117;