NM_012120.3:c.4+262T>G

Variant names:

• chr6-47478510-T-G
• rs13214158
• NM_012120.3:c.4+262T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012120.3(CD2AP):​c.4+262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,142 control chromosomes in the GnomAD database, including 5,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5549 hom., cov: 31)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• 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: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• inherited focal segmental glomerulosclerosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-47478510-T-G is Benign according to our data. Variant chr6-47478510-T-G is described in ClinVar as Benign. ClinVar VariationId is 1273719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.4+262T>G		intron	N/A	NP_036252.1	Q9Y5K6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.4+262T>G		intron	N/A	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000865253.1		c.4+262T>G		intron	N/A	ENSP00000535312.1
	CD2AP	ENST00000931707.1		c.4+262T>G		intron	N/A	ENSP00000601766.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38341 AN: 151030 Hom.: 5538 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.254 AC: 38373 AN: 151142 Hom.: 5549 Cov.: 31 AF XY: 0.263 AC XY: 19410 AN XY: 73842

African (AFR) AF: 0.199 AC: 8223 AN: 41308

American (AMR) AF: 0.376 AC: 5703 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 535 AN: 3462

East Asian (EAS) AF: 0.597 AC: 3015 AN: 5050

South Asian (SAS) AF: 0.216 AC: 1032 AN: 4778

European-Finnish (FIN) AF: 0.321 AC: 3333 AN: 10384

Middle Eastern (MID) AF: 0.171 AC: 49 AN: 286

European-Non Finnish (NFE) AF: 0.232 AC: 15706 AN: 67682

Other (OTH) AF: 0.236 AC: 497 AN: 2106

Alfa AF: 0.203 Hom.: 1217

Bravo AF: 0.261

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-1.0
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: rs13214158; hg19: chr6-47446246;