6-47479305-T-A

Position:

• chr6-47479305-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012120.3(CD2AP):​c.4+1057T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,088 control chromosomes in the GnomAD database, including 4,075 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4075 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.4+1057T>A		intron_variant		ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.4+1057T>A		intron_variant			XP_005249033.1
CD2AP	XM_017010641.2	c.4+1057T>A		intron_variant			XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.4+1057T>A		intron_variant		1	NM_012120.3	ENSP00000352264	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34454 AN: 151970 Hom.: 4071 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34477 AN: 152088 Hom.: 4075 Cov.: 32 AF XY: 0.222 AC XY: 16498 AN XY: 74352

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.227

Alfa AF: 0.246 Hom.: 608

Bravo AF: 0.227

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs4715019; hg19: chr6-47447041;