chr6-47586732-T-G

Variant names:

• chr6-47586732-T-G
• rs9369717
• NM_012120.3:c.1108+4667T>G

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+4667T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,988 control chromosomes in the GnomAD database, including 3,900 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 0.22 (3900 hom., cov: 32)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 9 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 = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.1108+4667T>G		intron_variant	Intron 11 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.1096+4667T>G		intron_variant	Intron 11 of 17		XP_005249033.1
CD2AP	XM_011514449.3	c.961+4667T>G		intron_variant	Intron 10 of 16		XP_011512751.1
CD2AP	XM_017010641.2	c.1108+4667T>G		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+4667T>G		intron_variant	Intron 11 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33622 AN: 151870 Hom.: 3896 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.221 AC: 33644 AN: 151988 Hom.: 3900 Cov.: 32 AF XY: 0.216 AC XY: 16060 AN XY: 74290

African (AFR) AF: 0.175 AC: 7272 AN: 41440

American (AMR) AF: 0.211 AC: 3223 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3466

East Asian (EAS) AF: 0.138 AC: 714 AN: 5170

South Asian (SAS) AF: 0.183 AC: 883 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2019 AN: 10560

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18047 AN: 67946

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.231 Hom.: 650

Bravo AF: 0.222

Asia WGS AF: 0.169 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.40
PhyloP100		0.49
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: rs9369717; hg19: chr6-47554468;