rs2894740

Variant names:

• chr6-47614105-A-G
• rs2894740
• NM_012120.3:c.1878+1569A>G

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+1569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,038 control chromosomes in the GnomAD database, including 8,571 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 0.31 (8571 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.1878+1569A>G		intron	N/A	NP_036252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.1878+1569A>G		intron	N/A	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47544 AN: 151922 Hom.: 8570 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.313 AC: 47541 AN: 152038 Hom.: 8571 Cov.: 32 AF XY: 0.309 AC XY: 22996 AN XY: 74302

African (AFR) AF: 0.146 AC: 6058 AN: 41488

American (AMR) AF: 0.271 AC: 4136 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3470

East Asian (EAS) AF: 0.159 AC: 823 AN: 5180

South Asian (SAS) AF: 0.407 AC: 1954 AN: 4806

European-Finnish (FIN) AF: 0.393 AC: 4141 AN: 10540

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27736 AN: 67968

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.374 Hom.: 11928

Bravo AF: 0.294

Asia WGS AF: 0.266 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.73
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: rs2894740; hg19: chr6-47581841;