rs9369717

chr6-47586732-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012120.3(CD2AP):c.1108+4667T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,988 control chromosomes in the GnomAD database, including 3,900 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 0.22 (3900 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.1108+4667T>G		intron_variant		ENST00000359314.5
CD2AP	XM_005248976.2	c.1096+4667T>G		intron_variant
CD2AP	XM_011514449.3	c.961+4667T>G		intron_variant
CD2AP	XM_017010641.2	c.1108+4667T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5	c.1108+4667T>G		intron_variant		1	NM_012120.3	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33622 AN: 151870 Hom.: 3896 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.221 AC: 33644 AN: 151988 Hom.: 3900 Cov.: 32 AF XY: 0.216 AC XY: 16060 AN XY: 74290

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.220

Alfa AF: 0.232 Hom.: 633

Bravo AF: 0.222

Asia WGS AF: 0.169 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.1
Dann	Benign	0.40

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: rs9369717; hg19: chr6-47554468;