rs719856

Variant names:

• chr6-47626986-G-A
• rs719856
• NM_012120.3:c.*2759G>A

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.*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
• Publications: 10 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: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.82).
• BP6: Variant 6-47626986-G-A is Benign according to our data. Variant chr6-47626986-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.*2759G>A		3_prime_UTR	Exon 18 of 18	NP_036252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.*2759G>A		3_prime_UTR	Exon 18 of 18	ENSP00000352264.5

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.317 AC: 135 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.183 AC: 7565 AN: 41340

American (AMR) AF: 0.375 AC: 5715 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3464

East Asian (EAS) AF: 0.601 AC: 3107 AN: 5166

South Asian (SAS) AF: 0.219 AC: 1052 AN: 4798

European-Finnish (FIN) AF: 0.328 AC: 3437 AN: 10466

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15780 AN: 67762

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.236 Hom.: 2562

Bravo AF: 0.255

Asia WGS AF: 0.397 AC: 1374 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 3, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.47
PhyloP100		0.096
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs719856; hg19: chr6-47594722;