2-30736519-C-A

Variant names:

• chr2-30736519-C-A
• rs368618651
• NM_144575.3:c.1706G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144575.3(CAPN13):​c.1706G>T​(p.Arg569Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R569H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPN13 NM_144575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144575.3. 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
	CAPN13	NM_144575.3	MANE Select	c.1706G>T	p.Arg569Leu	missense	Exon 18 of 23	NP_653176.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN13	ENST00000295055.12	TSL:5 MANE Select	c.1706G>T	p.Arg569Leu	missense	Exon 18 of 23	ENSP00000295055.8	Q6MZZ7-1
	CAPN13	ENST00000946473.1		c.1706G>T	p.Arg569Leu	missense	Exon 19 of 24	ENSP00000616532.1
	CAPN13	ENST00000946475.1		c.1706G>T	p.Arg569Leu	missense	Exon 19 of 24	ENSP00000616534.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.31
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.083
Sift	Benign	0.038	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.55		Loss of MoRF binding (P = 0.007)
MVP		0.18
MPC		0.091
ClinPred		0.57	D
GERP RS		1.6
Varity_R		0.46
gMVP		0.30
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs368618651; hg19: chr2-30959385;