NM_012120.3:c.4+5899C>T

Variant names:

• chr6-47484147-C-T
• rs9296558
• NM_012120.3:c.4+5899C>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.4+5899C>T 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 151,758 control chromosomes in the GnomAD database, including 4,208 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 (4208 hom., cov: 30)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 14 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=-0.89).
• 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+5899C>T		intron_variant	Intron 1 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.4+5899C>T		intron_variant	Intron 1 of 17		XP_005249033.1
CD2AP	XM_017010641.2	c.4+5899C>T		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+5899C>T		intron_variant	Intron 1 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35168 AN: 151640 Hom.: 4202 Cov.: 30

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.194

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: 0.232 AC: 35199 AN: 151758 Hom.: 4208 Cov.: 30 AF XY: 0.227 AC XY: 16843 AN XY: 74128

African (AFR) AF: 0.199 AC: 8233 AN: 41364

American (AMR) AF: 0.217 AC: 3308 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.137 AC: 707 AN: 5162

South Asian (SAS) AF: 0.206 AC: 991 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2030 AN: 10486

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

European-Non Finnish (NFE) AF: 0.271 AC: 18382 AN: 67886

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.250 Hom.: 1424

Bravo AF: 0.232

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.47
PhyloP100		-1.3
Mutation Taster		=99/1	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: rs9296558; hg19: chr6-47451883;