rs9296560

Variant names:

• chr6-47516315-G-C
• rs9296560
• NM_012120.3:c.165+12875G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• 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 rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.165+12875G>C		intron_variant	Intron 2 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.165+12875G>C		intron_variant	Intron 2 of 17		XP_005249033.1
CD2AP	XM_017010641.2	c.165+12875G>C		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.165+12875G>C		intron_variant	Intron 2 of 17	1	NM_012120.3	ENSP00000352264.5

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

African (AFR) AF: 0.555 AC: 23011 AN: 41460

American (AMR) AF: 0.519 AC: 7938 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2421 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1541 AN: 5178

South Asian (SAS) AF: 0.648 AC: 3127 AN: 4822

European-Finnish (FIN) AF: 0.589 AC: 6210 AN: 10548

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46739 AN: 67994

Other (OTH) AF: 0.635 AC: 1342 AN: 2112

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
PhyloP100		0.71
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: rs9296560; hg19: chr6-47484051;