rs9473132

chr6-47554621-G-Achr6-47554621-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012120.3(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 NM_012120.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.421-25G>A		intron_variant		ENST00000359314.5
CD2AP	XM_005248976.2	c.421-25G>A		intron_variant
CD2AP	XM_011514449.3	c.274-25G>A		intron_variant
CD2AP	XM_017010641.2	c.421-25G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91604 AN: 151846 Hom.: 28433 Cov.: 32

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

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.: 35 AF XY: 0.664 AC XY: 481604 AN XY: 725738

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.: 32 AF XY: 0.594 AC XY: 44145 AN XY: 74292

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Other links and lift over

dbSNP: rs9473132; hg19: chr6-47522357; COSMIC: COSV63761683;