Variant rs9473132 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 ENST00000359314.5(CD2AP):c.421-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,610,834 control chromosomes in the GnomAD database, including 353,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28445 hom., cov: 32)

Exomes 𝑓: 0.66 ( 324628 hom. )

Consequence

CD2AP
ENST00000359314.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.316

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=-0.84).

BP6

Variant 6-47554621-G-A is Benign according to our data. Variant chr6-47554621-G-A is described in ClinVar as [Benign]. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CD2AP	NM_012120.3 linkuse as main transcript	c.421-25G>A	intron_variant	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2 linkuse as main transcript	c.421-25G>A	intron_variant		XP_005249033.1
CD2AP	XM_011514449.3 linkuse as main transcript	c.274-25G>A	intron_variant		XP_011512751.1
CD2AP	XM_017010641.2 linkuse as main transcript	c.421-25G>A	intron_variant		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5 linkuse as main transcript	c.421-25G>A		intron_variant		1	NM_012120.3	ENSP00000352264	P1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91604

AN:

151846

Hom.:

28433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.698

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.628

GnomAD3 exomes

AF:

0.606

AC:

151993

AN:

250642

Hom.:

48240

AF XY:

0.620

AC XY:

83962

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.469

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.647

GnomAD4 exome

AF:

0.662

AC:

965671

AN:

1458870

Hom.:

324628

Cov.:

AF XY:

0.664

AC XY:

481604

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.701

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.603

AC:

91656

AN:

151964

Hom.:

28445

Cov.:

AF XY:

0.594

AC XY:

44145

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.528

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.698

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.686

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.601

Hom.:

3682

Bravo

AF:

0.593

Asia WGS

AF:

0.476

AC:

1654

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 69. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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