rs9296559

Variant names:

• chr6-47484534-T-C
• rs9296559
• NM_012120.3:c.4+6286T>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.4+6286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,188 control chromosomes in the GnomAD database, including 4,217 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 (4217 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 40 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.4+6286T>C		intron	N/A	NP_036252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.4+6286T>C		intron	N/A	ENSP00000352264.5
	CD2AP	ENST00000865253.1		c.4+6286T>C		intron	N/A	ENSP00000535312.1
	CD2AP	ENST00000931707.1		c.4+6286T>C		intron	N/A	ENSP00000601766.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35225 AN: 152068 Hom.: 4211 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.232 AC: 35257 AN: 152188 Hom.: 4217 Cov.: 32 AF XY: 0.227 AC XY: 16892 AN XY: 74420

African (AFR) AF: 0.199 AC: 8254 AN: 41518

American (AMR) AF: 0.217 AC: 3315 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3470

East Asian (EAS) AF: 0.138 AC: 715 AN: 5178

South Asian (SAS) AF: 0.206 AC: 995 AN: 4824

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10602

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

European-Non Finnish (NFE) AF: 0.270 AC: 18387 AN: 67984

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.257 Hom.: 6783

Bravo AF: 0.232

Asia WGS AF: 0.179 AC: 623 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		0.27
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: rs9296559; hg19: chr6-47452270;