6-47478075-TAGG-T

Position:

• chr6-47478075-TAGG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012120.3(CD2AP):​c.-167_-165del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 829,872 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0079 (23 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.875

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-DT (HGNC:55263): (CD2AP divergent transcript)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-47478075-TAGG-T is Benign according to our data. Variant chr6-47478075-TAGG-T is described in ClinVar as [Likely_benign]. Clinvar id is 357159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00638 (968/151838) while in subpopulation NFE AF= 0.00961 (652/67854). AF 95% confidence interval is 0.009. There are 4 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.-167_-165del		5_prime_UTR_variant	1/18	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.-167_-165del		5_prime_UTR_variant	1/18		XP_005249033.1
CD2AP	XM_017010641.2	c.-167_-165del		5_prime_UTR_variant	1/14		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.-167_-165del		5_prime_UTR_variant	1/18	1	NM_012120.3	ENSP00000352264	P1
CD2AP-DT	ENST00000604014.2	n.83_85del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 969 AN: 151718 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.00673

GnomAD4 exome AF: 0.00791 AC: 5363 AN: 678034 Hom.: 23 AF XY: 0.00770 AC XY: 2725 AN XY: 353862

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00370

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00306

Gnomad4 FIN exome AF: 0.00292

Gnomad4 NFE exome AF: 0.00989

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00638 AC: 968 AN: 151838 Hom.: 4 Cov.: 33 AF XY: 0.00613 AC XY: 455 AN XY: 74226

Gnomad4 AFR AF: 0.00239

Gnomad4 AMR AF: 0.00687

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00246

Gnomad4 NFE AF: 0.00961

Gnomad4 OTH AF: 0.00666

Alfa AF: 0.00667 Hom.: 0

Bravo AF: 0.00646

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs533900030; hg19: chr6-47445811;