rs76153148

Variant names:

• chr6-47576998-C-A
• rs76153148
• NM_012120.3:c.809-11C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-47576998-C-A
• chr6-47576998-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_012120.3(CD2AP):​c.809-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,311,452 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (57 hom.)
• Consequence: CD2AP NM_012120.3 intron
• Scores: Splicing: ADA: 0.005442
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.529
• Publications: 2 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 6-47576998-C-A is Benign according to our data. Variant chr6-47576998-C-A is described in ClinVar as Benign. ClinVar VariationId is 260193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0511 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.809-11C>A		intron	N/A	NP_036252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.809-11C>A		intron	N/A	ENSP00000352264.5
	CD2AP	ENST00000865253.1		c.812-11C>A		intron	N/A	ENSP00000535312.1
	CD2AP	ENST00000931707.1		c.809-11C>A		intron	N/A	ENSP00000601766.1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152054 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00652

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00352 AC: 882 AN: 250852 AF XY: 0.00331

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0412

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00212 AC: 2463 AN: 1159280 Hom.: 57 Cov.: 17 AF XY: 0.00203 AC XY: 1200 AN XY: 592302

African (AFR) AF: 0.00 AC: 0 AN: 27674

American (AMR) AF: 0.0000451 AC: 2 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24150

East Asian (EAS) AF: 0.0530 AC: 2022 AN: 38150

South Asian (SAS) AF: 0.000175 AC: 14 AN: 80004

European-Finnish (FIN) AF: 0.00370 AC: 197 AN: 53218

Middle Eastern (MID) AF: 0.000580 AC: 3 AN: 5176

European-Non Finnish (NFE) AF: 0.000153 AC: 128 AN: 836306

Other (OTH) AF: 0.00193 AC: 97 AN: 50270

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152172 Hom.: 7 Cov.: 32 AF XY: 0.00229 AC XY: 170 AN XY: 74396

African (AFR) AF: 0.0000241 AC: 1 AN: 41530

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0386 AC: 200 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00652 AC: 69 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67978

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00174 Hom.: 14

Bravo AF: 0.00152

Asia WGS AF: 0.0140 AC: 50 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 3, susceptibility to (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.5
DANN	Benign	0.74
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0054
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.020		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: rs76153148; hg19: chr6-47544734;