rs2953171

Variant names:

• chr2-240596636-C-T
• rs2953171
• NM_023083.4:c.1482-45C>T

Variant summary

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

The NM_023083.4(CAPN10):​c.1482-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,528,980 control chromosomes in the GnomAD database, including 24,785 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 0.17 (2319 hom., cov: 34)
  • Exomes 𝑓: 0.18 (22466 hom.)
• Consequence: CAPN10 NM_023083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	NM_023083.4	MANE Select	c.1482-45C>T		intron	N/A	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.1279-1252C>T		intron	N/A	NP_075573.3	Q9HC96-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.1482-45C>T		intron	N/A	ENSP00000375844.2	Q9HC96-1
	CAPN10	ENST00000354082.8	TSL:1	c.1279-1252C>T		intron	N/A	ENSP00000270362.6	Q9HC96-3
	CAPN10	ENST00000352879.8	TSL:1	c.142-1252C>T		intron	N/A	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25451 AN: 152134 Hom.: 2323 Cov.: 34

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.194 AC: 34865 AN: 179982 AF XY: 0.191

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.0976

Gnomad EAS exome AF: 0.281

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.177 AC: 243797 AN: 1376728 Hom.: 22466 Cov.: 34 AF XY: 0.177 AC XY: 119267 AN XY: 675466

African (AFR) AF: 0.113 AC: 3484 AN: 30904

American (AMR) AF: 0.257 AC: 8616 AN: 33484

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 1978 AN: 20700

East Asian (EAS) AF: 0.308 AC: 11962 AN: 38880

South Asian (SAS) AF: 0.198 AC: 14378 AN: 72588

European-Finnish (FIN) AF: 0.222 AC: 10577 AN: 47682

Middle Eastern (MID) AF: 0.149 AC: 737 AN: 4958

European-Non Finnish (NFE) AF: 0.170 AC: 182376 AN: 1070918

Other (OTH) AF: 0.171 AC: 9689 AN: 56614

GnomAD4 genome AF: 0.167 AC: 25458 AN: 152252 Hom.: 2319 Cov.: 34 AF XY: 0.172 AC XY: 12817 AN XY: 74446

African (AFR) AF: 0.115 AC: 4767 AN: 41550

American (AMR) AF: 0.225 AC: 3446 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1497 AN: 5162

South Asian (SAS) AF: 0.206 AC: 995 AN: 4830

European-Finnish (FIN) AF: 0.220 AC: 2335 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11607 AN: 68004

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.164 Hom.: 556

Bravo AF: 0.165

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.80
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2953171; hg19: chr2-241536053; COSMIC: COSV54375298; COSMIC: COSV54375298;