Variant chr3-195279401-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012287.6(ACAP2):c.2264G>A(p.Arg755His) variant causes a missense change. The variant allele was found at a frequency of 0.0000747 in 1,605,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

ACAP2
NM_012287.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

ACAP2 (HGNC:16469): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 2) Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in ruffle. [provided by Alliance of Genome Resources, Apr 2022]

ACAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ACAP2	NM_012287.6 linkuse as main transcript	c.2264G>A	p.Arg755His	missense_variant	23/23	ENST00000326793.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAP2	ENST00000326793.11 linkuse as main transcript	c.2264G>A	p.Arg755His	missense_variant	23/23	1	NM_012287.6	P1
ACAP2	ENST00000472860.1 linkuse as main transcript	n.206G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000448

AC:

AN:

245676

Hom.:

AF XY:

0.0000451

AC XY:

AN XY:

132924

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000610

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000709

AC:

103

AN:

1453492

Hom.:

Cov.:

AF XY:

0.0000650

AC XY:

AN XY:

723162

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000758

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.000112

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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

Feb 11, 2022

The c.2264G>A (p.R755H) alteration is located in exon 23 (coding exon 23) of the ACAP2 gene. This alteration results from a G to A substitution at nucleotide position 2264, causing the arginine (R) at amino acid position 755 to be replaced by a histidine (H). 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

0.30

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.99

D;.

Vest4

0.35

MVP

0.50

MPC

1.4

ClinPred

0.30

GERP RS

5.2

Varity_R

0.43

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: 27

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