6-47478190-C-CAGG

Position:

• chr6-47478190-C-CAGG

Variant summary

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

The NM_012120.3(CD2AP):​c.-55_-54insAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,429,984 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (22 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.760

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 6-47478190-C-CAGG is Benign according to our data. Variant chr6-47478190-C-CAGG is described in ClinVar as [Likely_benign]. Clinvar id is 357161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00289 (440/152050) while in subpopulation SAS AF= 0.0124 (60/4822). AF 95% confidence interval is 0.00992. There are 1 homozygotes in gnomad4. There are 224 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.-55_-54insAGG		5_prime_UTR_variant	1/18	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.-55_-54insAGG		5_prime_UTR_variant	1/18		XP_005249033.1
CD2AP	XM_017010641.2	c.-55_-54insAGG		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.-55_-54insAGG		5_prime_UTR_variant	1/18	1	NM_012120.3	ENSP00000352264	P1
CD2AP-DT	ENST00000604014.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151944 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.000947

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00183

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00275 AC: 3515 AN: 1277934 Hom.: 22 Cov.: 41 AF XY: 0.00304 AC XY: 1924 AN XY: 632244

Gnomad4 AFR exome AF: 0.00374

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.0243

Gnomad4 EAS exome AF: 0.000667

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.000513

Gnomad4 NFE exome AF: 0.00165

Gnomad4 OTH exome AF: 0.00457

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152050 Hom.: 1 Cov.: 33 AF XY: 0.00301 AC XY: 224 AN XY: 74328

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.000947

Gnomad4 NFE AF: 0.00183

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000184 Hom.: 0

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs560930115; hg19: chr6-47445926;