7-116898780-C-T

Variant names:

• chr7-116898780-C-T
• NM_006136.3:c.164C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006136.3(CAPZA2):​c.164C>T​(p.Ala55Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPZA2 NM_006136.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

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]

CAPZA2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.8416 (below the threshold of 3.09). Trascript score misZ: 1.2445 (below the threshold of 3.09). GenCC associations: The gene is linked to complex neurodevelopmental disorder.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006136.3. 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
	CAPZA2	NM_006136.3	MANE Select	c.164C>T	p.Ala55Val	missense	Exon 4 of 10	NP_006127.1	A4D0V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZA2	ENST00000361183.8	TSL:1 MANE Select	c.164C>T	p.Ala55Val	missense	Exon 4 of 10	ENSP00000354947.2	P47755-1
	CAPZA2	ENST00000464223.5	TSL:1	c.97C>T	p.His33Tyr	missense	Exon 4 of 4	ENSP00000420640.1	C9JCZ4
	CAPZA2	ENST00000484325.1	TSL:1	c.97C>T	p.His33Tyr	missense	Exon 5 of 5	ENSP00000418262.1	C9J7V0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.68
Sift	Benign	0.031	D
Sift4G	Benign	0.074	T
Polyphen		0.93	P
Vest4		0.73
MutPred		0.56		Loss of helix (P = 0.079)
MVP		0.43
MPC		0.89
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.59
Mutation Taster		=24/76	disease causing

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

Other links and lift over

hg19: chr7-116538834;