2-30743449-G-C

Position:

• chr2-30743449-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144575.3(CAPN13):​c.1379C>G​(p.Ala460Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPN13 NM_144575.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.323

Genes affected

CAPN13 (HGNC:16663): (calpain 13) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes a member of the calpain large subunit family. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN13	NM_144575.3	c.1379C>G	p.Ala460Gly	missense_variant	13/23	ENST00000295055.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN13	ENST00000295055.12	c.1379C>G	p.Ala460Gly	missense_variant	13/23	5	NM_144575.3	P1
CAPN13	ENST00000465450.2	n.267C>G		non_coding_transcript_exon_variant	3/3	5
CAPN13	ENST00000450650.5	c.71C>G	p.Ala24Gly	missense_variant, NMD_transcript_variant	1/11	2
CAPN13	ENST00000458085.6	c.*63C>G		3_prime_UTR_variant, NMD_transcript_variant	14/16	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.1379C>G (p.A460G) alteration is located in exon 13 (coding exon 12) of the CAPN13 gene. This alteration results from a C to G substitution at nucleotide position 1379, causing the alanine (A) at amino acid position 460 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	7.1
DANN	Benign	0.95
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		0.48	P
Vest4		0.46
MutPred		0.71		Loss of sheet (P = 0.0817);
MVP		0.79
MPC		0.14
ClinPred		0.19	T
GERP RS		-0.67
Varity_R		0.11
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-30966315;