chr6-47614105-A-G

Position:

• chr6-47614105-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.1878+1569A>G		intron_variant		ENST00000359314.5
CD2AP	XM_005248976.2	c.1866+1569A>G		intron_variant
CD2AP	XM_011514449.3	c.1731+1569A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5	c.1878+1569A>G		intron_variant		1	NM_012120.3	P1

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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.342

Alfa AF: 0.388 Hom.: 9974

Bravo AF: 0.294

Asia WGS AF: 0.266 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2894740; hg19: chr6-47581841;