Variant 6-47478264-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012120.3(CD2AP):c.4+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,568,450 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 11 hom. )

Consequence

CD2AP
NM_012120.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.754

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=-0.88).

BP6

Variant 6-47478264-G-A is Benign according to our data. Variant chr6-47478264-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00188 (286/152262) while in subpopulation NFE AF= 0.00353 (240/68008). AF 95% confidence interval is 0.00316. There are 0 homozygotes in gnomad4. There are 124 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CD2AP	NM_012120.3 linkuse as main transcript	c.4+16G>A	intron_variant	ENST00000359314.5
CD2AP	XM_005248976.2 linkuse as main transcript	c.4+16G>A	intron_variant
CD2AP	XM_017010641.2 linkuse as main transcript	c.4+16G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5 linkuse as main transcript	c.4+16G>A		intron_variant		1	NM_012120.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

287

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00136

AC:

230

AN:

169264

Hom.:

AF XY:

0.00132

AC XY:

121

AN XY:

91622

show subpopulations

Gnomad AFR exome

AF:

0.000905

Gnomad AMR exome

AF:

0.000412

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000416

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00298

Gnomad OTH exome

AF:

0.00174

GnomAD4 exome

AF:

0.00335

AC:

4741

AN:

1416188

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2264

AN XY:

700276

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.000606

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.00413

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152262

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00353

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00193

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.8

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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