rs6936632

Variant names:

• chr6-47588297-G-A
• rs6936632
• NM_012120.3:c.1108+6232G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012120.3(CD2AP):​c.1108+6232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 152,054 control chromosomes in the GnomAD database, including 563 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 0.075 (563 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.1108+6232G>A		intron_variant	Intron 11 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.1096+6232G>A		intron_variant	Intron 11 of 17		XP_005249033.1
CD2AP	XM_011514449.3	c.961+6232G>A		intron_variant	Intron 10 of 16		XP_011512751.1
CD2AP	XM_017010641.2	c.1108+6232G>A		intron_variant	Intron 11 of 13		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.1108+6232G>A		intron_variant	Intron 11 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11336 AN: 151936 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0883

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0746 AC: 11339 AN: 152054 Hom.: 563 Cov.: 32 AF XY: 0.0734 AC XY: 5454 AN XY: 74330

African (AFR) AF: 0.0180 AC: 749 AN: 41518

American (AMR) AF: 0.0624 AC: 953 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 306 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1313 AN: 10566

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7660 AN: 67928

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0905 Hom.: 537

Bravo AF: 0.0677

Asia WGS AF: 0.0120 AC: 43 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		0.47
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: rs6936632; hg19: chr6-47556033;