chr6-17421665-G-A

Position:

• chr6-17421665-G-A

Variant summary

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

The NM_006366.3(CAP2):​c.110G>A​(p.Gly37Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAP2 NM_006366.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30

Genes affected

CAP2 (HGNC:20039): (cyclase associated actin cytoskeleton regulatory protein 2) This gene was identified by its similarity to the gene for human adenylyl cyclase-associated protein. The function of the protein encoded by this gene is unknown. However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin. [provided by RefSeq, Jul 2008]

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
CAP2	NM_006366.3	c.110G>A	p.Gly37Asp	missense_variant	2/13	ENST00000229922.7
CAP2	NM_001363534.2	c.110G>A	p.Gly37Asp	missense_variant	2/12
CAP2	NM_001363533.2	c.110G>A	p.Gly37Asp	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAP2	ENST00000229922.7	c.110G>A	p.Gly37Asp	missense_variant	2/13	1	NM_006366.3	P1

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

Jan 03, 2024

The c.110G>A (p.G37D) alteration is located in exon 2 (coding exon 1) of the CAP2 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T;.;T;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.;.;.;M;M
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.0	N;.;.;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.21	T;.;.;T;T;D;T
Sift4G	Benign	0.64	T;T;T;T;T;T;T
Polyphen		0.98	D;.;.;D;P;.;.
Vest4		0.40
MutPred		0.57		Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);Loss of catalytic residue at V38 (P = 0.0537);
MVP		0.54
MPC		0.57
ClinPred		0.86	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.71

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: chr6-17421896;