Variant chr6-17426592-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006366.3(CAP2):c.124G>A(p.Val42Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CAP2
NM_006366.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Variant links:

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]

CAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1543445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAP2	NM_006366.3 linkuse as main transcript	c.124G>A	p.Val42Met	missense_variant, splice_region_variant	3/13	ENST00000229922.7	NP_006357.1	P40123-1Q5JPJ8
CAP2	NM_001363534.2 linkuse as main transcript	c.124G>A	p.Val42Met	missense_variant, splice_region_variant	3/12		NP_001350463.1
CAP2	NM_001363533.2 linkuse as main transcript	c.124G>A	p.Val42Met	missense_variant, splice_region_variant	3/10		NP_001350462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAP2	ENST00000229922.7 linkuse as main transcript	c.124G>A	p.Val42Met	missense_variant, splice_region_variant	3/13	1	NM_006366.3	ENSP00000229922.2		P40123-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251446

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1460314

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726604

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.124G>A (p.V42M) alteration is located in exon 3 (coding exon 2) of the CAP2 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by a methionine (M). 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

0.097

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T;.;T;.;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.73

T;T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.15

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;.;.;.;.;M;M

MutationTaster

Benign

0.78

D;D;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.67

N;.;.;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.080

T;.;.;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T;T

Polyphen

0.81

P;.;.;D;B;.;.

Vest4

0.25

MutPred

0.46

Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);Gain of disorder (P = 0.0851);

MVP

0.20

MPC

0.71

ClinPred

0.37

GERP RS

4.7

Varity_R

0.053

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over