7-116862613-T-C

Position:

• chr7-116862613-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_006136.3(CAPZA2):​c.2T>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPZA2 NM_006136.3 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

CAPZA2 (HGNC:1490): (capping actin protein of muscle Z-line subunit alpha 2) The protein encoded by this gene is a member of the F-actin capping protein alpha subunit family. It is the alpha subunit of the barbed-end actin binding protein Cap Z. By capping the barbed end of actin filaments, Cap Z regulates the growth of the actin filaments at the barbed end. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA2	NM_006136.3	c.2T>C	p.Met1?	start_lost	1/10	ENST00000361183.8	NP_006127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPZA2	ENST00000361183.8	c.2T>C	p.Met1?	start_lost	1/10	1	NM_006136.3	ENSP00000354947.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2024

Not observed at significant frequency in large population cohorts (gnomAD); De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Initiation codon variant in a gene for which loss-of-function is not an established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.72	T
PROVEAN	Uncertain	-3.1	D;.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0030	D;.;D
Polyphen		0.72	P;.;.
Vest4		0.88
MutPred		0.74		Gain of glycosylation at M1 (P = 0.0183);Gain of glycosylation at M1 (P = 0.0183);Gain of glycosylation at M1 (P = 0.0183);
MVP		0.73
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.89
gMVP		0.65

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: chr7-116502667;