rs6940729

Positions:

• chr6-47585184-T-A
• chr6-47585184-T-C
• chr6-47585184-T-G

Variant summary

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

The NM_012120.3(CD2AP):​c.1108+3119T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 149,864 control chromosomes in the GnomAD database, including 28,227 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 (28227 hom., cov: 28)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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=-0.92).
• 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	Protein	UniProt
CD2AP	NM_012120.3	c.1108+3119T>A		intron_variant		ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.1096+3119T>A		intron_variant			XP_005249033.1
CD2AP	XM_011514449.3	c.961+3119T>A		intron_variant			XP_011512751.1
CD2AP	XM_017010641.2	c.1108+3119T>A		intron_variant			XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.1108+3119T>A		intron_variant		1	NM_012120.3	ENSP00000352264	P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 90706 AN: 149770 Hom.: 28217 Cov.: 28

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.606 AC: 90751 AN: 149864 Hom.: 28227 Cov.: 28 AF XY: 0.597 AC XY: 43620 AN XY: 73080

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.629

Alfa AF: 0.624 Hom.: 3506

Bravo AF: 0.593

Asia WGS AF: 0.472 AC: 1635 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.53

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: rs6940729; hg19: chr6-47552920;