2-240587011-C-T

Variant names:

• chr2-240587011-C-T
• rs138005500
• NM_023083.4:c.100C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_023083.4(CAPN10):​c.100C>T​(p.Leu34Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,323,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CAPN10 NM_023083.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.

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.100C>T	p.Leu34Leu	synonymous	Exon 1 of 12	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.100C>T	p.Leu34Leu	synonymous	Exon 1 of 10	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.100C>T	p.Leu34Leu	synonymous	Exon 1 of 12	ENSP00000375844.2	Q9HC96-1
	CAPN10	ENST00000354082.8	TSL:1	c.100C>T	p.Leu34Leu	synonymous	Exon 1 of 10	ENSP00000270362.6	Q9HC96-3
	CAPN10	ENST00000352879.8	TSL:1	c.100C>T	p.Leu34Leu	synonymous	Exon 1 of 4	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1323522 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 652260

African (AFR) AF: 0.00 AC: 0 AN: 26990

American (AMR) AF: 0.00 AC: 0 AN: 25980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23394

East Asian (EAS) AF: 0.00 AC: 0 AN: 28288

South Asian (SAS) AF: 0.00 AC: 0 AN: 71780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4996

European-Non Finnish (NFE) AF: 9.59e-7 AC: 1 AN: 1042674

Other (OTH) AF: 0.00 AC: 0 AN: 54396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		2.2
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism

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: rs138005500; hg19: chr2-241526428;