rs9349407

Variant names:

• chr6-47485642-G-C
• rs9349407
• NM_012120.3:c.4+7394G>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+7394G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,052 control chromosomes in the GnomAD database, including 4,169 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 (4169 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 116 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.4+7394G>C		intron_variant	Intron 1 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.4+7394G>C		intron_variant	Intron 1 of 17		XP_005249033.1
CD2AP	XM_017010641.2	c.4+7394G>C		intron_variant	Intron 1 of 13		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.4+7394G>C		intron_variant	Intron 1 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34998 AN: 151934 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.230 AC: 35025 AN: 152052 Hom.: 4169 Cov.: 32 AF XY: 0.225 AC XY: 16762 AN XY: 74340

African (AFR) AF: 0.194 AC: 8025 AN: 41466

American (AMR) AF: 0.216 AC: 3304 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3468

East Asian (EAS) AF: 0.139 AC: 717 AN: 5172

South Asian (SAS) AF: 0.206 AC: 990 AN: 4812

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10582

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

European-Non Finnish (NFE) AF: 0.271 AC: 18399 AN: 67948

Other (OTH) AF: 0.229 AC: 484 AN: 2114

Alfa AF: 0.248 Hom.: 619

Bravo AF: 0.231

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9349407; hg19: chr6-47453378;