Variant rs9473135 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012120.3(CD2AP):c.1275-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,607,680 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 206 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 203 hom. )

Consequence

CD2AP
NM_012120.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.396

Variant links:

Genes affected

CD2AP (HGNC:14258): (CD2 associated protein) This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety of cell membrane proteins through multiple actin binding sites, SH3 domains, and a proline-rich region containing binding sites for SH3 domains. The cytoplasmic protein localizes to membrane ruffles, lipid rafts, and the leading edges of cells. It is implicated in dynamic actin remodeling and membrane trafficking that occurs during receptor endocytosis and cytokinesis. Haploinsufficiency of this gene is implicated in susceptibility to glomerular disease. [provided by RefSeq, Jul 2008]

CD2AP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-47599281-G-A is Benign according to our data. Variant chr6-47599281-G-A is described in ClinVar as [Benign]. Clinvar id is 260183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CD2AP	NM_012120.3 linkuse as main transcript	c.1275-20G>A	intron_variant	ENST00000359314.5
CD2AP	XM_005248976.2 linkuse as main transcript	c.1263-20G>A	intron_variant
CD2AP	XM_011514449.3 linkuse as main transcript	c.1128-20G>A	intron_variant
CD2AP	XM_017010641.2 linkuse as main transcript	c.1275-20G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5 linkuse as main transcript	c.1275-20G>A		intron_variant		1	NM_012120.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4516

AN:

151826

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.0307

GnomAD3 exomes

AF:

0.00993

AC:

2465

AN:

248296

Hom.:

AF XY:

0.00821

AC XY:

1105

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.00984

Gnomad ASJ exome

AF:

0.0288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.00485

AC:

7063

AN:

1455736

Hom.:

203

Cov.:

AF XY:

0.00450

AC XY:

3257

AN XY:

724482

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0297

AC:

4517

AN:

151944

Hom.:

206

Cov.:

AF XY:

0.0280

AC XY:

2083

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0952

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.0304

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0345

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.094

DANN

Benign

0.53

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