rs9296560

chr6-47516315-G-C

Variant summary

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

The NM_012120.3(CD2AP):c.165+12875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,066 control chromosomes in the GnomAD database, including 29,243 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 0.61 (29243 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.165+12875G>C		intron_variant		ENST00000359314.5
CD2AP	XM_005248976.2	c.165+12875G>C		intron_variant
CD2AP	XM_017010641.2	c.165+12875G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5	c.165+12875G>C		intron_variant		1	NM_012120.3	P1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93051 AN: 151948 Hom.: 29231 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.612 AC: 93105 AN: 152066 Hom.: 29243 Cov.: 32 AF XY: 0.604 AC XY: 44865 AN XY: 74334

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.635

Alfa AF: 0.639 Hom.: 3910

Bravo AF: 0.602

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	12
Dann	Benign	0.66

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: rs9296560; hg19: chr6-47484051;