rs9349417

Variant names:

• chr6-47612921-A-G
• rs9349417
• NM_012120.3:c.1878+385A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-47612921-A-G
• chr6-47612921-A-T

Variant summary

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

The NM_012120.3(CD2AP):​c.1878+385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,050 control chromosomes in the GnomAD database, including 5,505 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 0.26 (5505 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.1878+385A>G		intron_variant	Intron 17 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.1866+385A>G		intron_variant	Intron 17 of 17		XP_005249033.1
CD2AP	XM_011514449.3	c.1731+385A>G		intron_variant	Intron 16 of 16		XP_011512751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.1878+385A>G		intron_variant	Intron 17 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40251 AN: 151932 Hom.: 5498 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.265 AC: 40293 AN: 152050 Hom.: 5505 Cov.: 32 AF XY: 0.259 AC XY: 19265 AN XY: 74346

African (AFR) AF: 0.312 AC: 12942 AN: 41472

American (AMR) AF: 0.231 AC: 3526 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3466

East Asian (EAS) AF: 0.137 AC: 711 AN: 5176

South Asian (SAS) AF: 0.206 AC: 993 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.272 AC: 18451 AN: 67936

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.266 Hom.: 2810

Bravo AF: 0.271

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.69
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9349417; hg19: chr6-47580657; COSMIC: COSV63762674; COSMIC: COSV63762674;