2-240594824-AGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT-AGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT

Variant names:

• chr2-240594824-A-AGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT
• rs3842570
• NM_023083.4:c.998-148_998-147insCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_023083.4(CAPN10):​c.998-148_998-147insCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 135,024 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 37)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAPN10 NM_023083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 26 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: Uncertain_significance. The variant received 0 ACMG points.

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.998-148_998-147insCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGC		intron	N/A	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.998-148_998-147insCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGC		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.997+115_997+116insGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT		intron	N/A	ENSP00000375844.2	Q9HC96-1
	CAPN10	ENST00000354082.8	TSL:1	c.997+115_997+116insGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT		intron	N/A	ENSP00000270362.6	Q9HC96-3
	CAPN10	ENST00000352879.8	TSL:1	c.142-3064_142-3063insGATGATTCTGTCCCAGGAGCCGGGAGGAGGGTGATGATTCTGTCCCAGGAGCCGGGAGGAGGGT		intron	N/A	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes AF: 0.0000296 AC: 4 AN: 135024 Hom.: 0 Cov.: 37

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000650

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000197 AC: 13 AN: 660404 Hom.: 0 AF XY: 0.0000148 AC XY: 5 AN XY: 337148

African (AFR) AF: 0.00 AC: 0 AN: 20758

American (AMR) AF: 0.00 AC: 0 AN: 22902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15098

East Asian (EAS) AF: 0.0000311 AC: 1 AN: 32202

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 51992

European-Finnish (FIN) AF: 0.0000302 AC: 1 AN: 33074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2480

European-Non Finnish (NFE) AF: 0.0000223 AC: 10 AN: 449178

Other (OTH) AF: 0.00 AC: 0 AN: 32720

GnomAD4 genome AF: 0.0000296 AC: 4 AN: 135024 Hom.: 0 Cov.: 37 AF XY: 0.0000308 AC XY: 2 AN XY: 64924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 37210

American (AMR) AF: 0.00 AC: 0 AN: 13342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3214

East Asian (EAS) AF: 0.00 AC: 0 AN: 4368

South Asian (SAS) AF: 0.00 AC: 0 AN: 3868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000650 AC: 4 AN: 61584

Other (OTH) AF: 0.00 AC: 0 AN: 1792

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0259881), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.043

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3842570;

hg19: chr2-241534241;