rs719856

Positions:

• chr6-47626986-G-A

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.*2759G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,980 control chromosomes in the GnomAD database, including 5,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5489 hom., cov: 32)
  • Exomes 𝑓: 0.32 (16 hom.)
• Consequence: CD2AP NM_012120.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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=-0.82).
• BP6: Variant 6-47626986-G-A is Benign according to our data. Variant chr6-47626986-G-A is described in ClinVar as [Benign]. Clinvar id is 357234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2AP	NM_012120.3	c.*2759G>A		3_prime_UTR_variant	18/18	ENST00000359314.5
CD2AP	XM_005248976.2	c.*2759G>A		3_prime_UTR_variant	18/18
CD2AP	XM_011514449.3	c.*2759G>A		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2AP	ENST00000359314.5	c.*2759G>A		3_prime_UTR_variant	18/18	1	NM_012120.3	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 37987 AN: 151428 Hom.: 5479 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.317 AC: 137 AN: 432 Hom.: 16 Cov.: 0 AF XY: 0.304 AC XY: 79 AN XY: 260

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.251 AC: 38016 AN: 151548 Hom.: 5489 Cov.: 32 AF XY: 0.260 AC XY: 19288 AN XY: 74050

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.232

Alfa AF: 0.235 Hom.: 1550

Bravo AF: 0.255

Asia WGS AF: 0.397 AC: 1374 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis 3, susceptibility to Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs719856; hg19: chr6-47594722;