7-116917772-A-G

Position:

• chr7-116917772-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_006136.3(CAPZA2):​c.766A>G​(p.Lys256Glu) variant causes a missense change involving the alteration of a 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 Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPZA2 NM_006136.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 9.28

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 Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945
• PP5: Variant 7-116917772-A-G is Pathogenic according to our data. Variant chr7-116917772-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 830217.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA2	NM_006136.3	c.766A>G	p.Lys256Glu	missense_variant	10/10	ENST00000361183.8	NP_006127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPZA2	ENST00000361183.8	c.766A>G	p.Lys256Glu	missense_variant	10/10	1	NM_006136.3	ENSP00000354947	P1
CAPZA2	ENST00000426421.5	c.*261A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	5		ENSP00000395395
CAPZA2	ENST00000496161.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital

Mar 16, 2020

This variant exerted loss of function effect in Drosophila. -

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Nov 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	3.6	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.81		Loss of MoRF binding (P = 0.0014);
MVP		0.72
MPC		3.9
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.90
gMVP		0.94

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

LitVar

Other links and lift over

dbSNP: rs1791701214; hg19: chr7-116557826;