6-47581390-C-T

Variant names:

• chr6-47581390-C-T
• rs9296566
• NM_012120.3:c.1045+490C>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.1045+490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,874 control chromosomes in the GnomAD database, including 28,569 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 0.60 (28569 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 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.1045+490C>T		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.1045+490C>T		intron	N/A	ENSP00000352264.5
	CD2AP	ENST00000479857.1	TSL:3	n.133+490C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91782 AN: 151756 Hom.: 28556 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.605 AC: 91835 AN: 151874 Hom.: 28569 Cov.: 32 AF XY: 0.596 AC XY: 44249 AN XY: 74204

African (AFR) AF: 0.529 AC: 21899 AN: 41424

American (AMR) AF: 0.516 AC: 7877 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2425 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3125 AN: 4808

European-Finnish (FIN) AF: 0.590 AC: 6204 AN: 10512

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46670 AN: 67904

Other (OTH) AF: 0.628 AC: 1323 AN: 2108

Alfa AF: 0.631 Hom.: 3962

Bravo AF: 0.593

Asia WGS AF: 0.475 AC: 1643 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.89
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: rs9296566; hg19: chr6-47549126;