6-17507680-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006366.3(CAP2):c.484G>A(p.Ala162Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: CAP2 NM_006366.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.62

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]

LOC101928491 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAP2	NM_006366.3	c.484G>A	p.Ala162Thr	missense_variant	6/13	ENST00000229922.7
LOC101928491	NR_110855.1	n.282+893C>T		intron_variant, non_coding_transcript_variant
CAP2	NM_001363534.2	c.406G>A	p.Ala136Thr	missense_variant	5/12
CAP2	NM_001363533.2	c.301-31589G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAP2	ENST00000229922.7	c.484G>A	p.Ala162Thr	missense_variant	6/13	1	NM_006366.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251462 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1459240 Hom.: 0 Cov.: 28 AF XY: 0.00000964 AC XY: 7 AN XY: 726142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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

Nov 18, 2022

The c.484G>A (p.A162T) alteration is located in exon 6 (coding exon 5) of the CAP2 gene. This alteration results from a G to A substitution at nucleotide position 484, causing the alanine (A) at amino acid position 162 to be replaced by a threonine (T). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.066	T;T
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.83		Loss of ubiquitination at K157 (P = 0.1388);.;
MVP		0.51
MPC		0.87
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.44
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: -39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs778806530; hg19: chr6-17507911; COSMIC: COSV57733543;