rs10948363

Variant names:

• chr6-47520026-A-G
• rs10948363
• NM_012120.3:c.166-13576A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012120.3(CD2AP):​c.166-13576A>G 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 152,110 control chromosomes in the GnomAD database, including 4,073 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 (4073 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 117 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 3, susceptibility to

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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 rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.166-13576A>G		intron_variant	Intron 2 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.166-13576A>G		intron_variant	Intron 2 of 17		XP_005249033.1
CD2AP	XM_017010641.2	c.166-13576A>G		intron_variant	Intron 2 of 13		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.166-13576A>G		intron_variant	Intron 2 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34434 AN: 151992 Hom.: 4069 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.227 AC: 34456 AN: 152110 Hom.: 4073 Cov.: 32 AF XY: 0.222 AC XY: 16485 AN XY: 74358

African (AFR) AF: 0.181 AC: 7521 AN: 41514

American (AMR) AF: 0.215 AC: 3284 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3466

East Asian (EAS) AF: 0.138 AC: 714 AN: 5174

South Asian (SAS) AF: 0.205 AC: 989 AN: 4822

European-Finnish (FIN) AF: 0.193 AC: 2034 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18387 AN: 67958

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.250 Hom.: 7691

Bravo AF: 0.227

Asia WGS AF: 0.174 AC: 605 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10948363; hg19: chr6-47487762;