6-47478510-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.4+262T>G		intron_variant		ENST00000359314.5
CD2AP	XM_005248976.2	c.4+262T>G		intron_variant
CD2AP	XM_017010641.2	c.4+262T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5	c.4+262T>G		intron_variant		1	NM_012120.3	P1

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

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.236

Alfa AF: 0.176 Hom.: 531

Bravo AF: 0.261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs13214158; hg19: chr6-47446246;