rs9473132

Variant names:

• chr6-47554621-G-A
• rs9473132
• NM_012120.3:c.421-25G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-47554621-G-A
• chr6-47554621-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012120.3(CD2AP):​c.421-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,610,834 control chromosomes in the GnomAD database, including 353,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28445 hom., cov: 32)
  • Exomes 𝑓: 0.66 (324628 hom.)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-47554621-G-A is Benign according to our data. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47554621-G-A is described in CliVar as Benign. Clinvar id is 1289128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3	c.421-25G>A		intron_variant	Intron 4 of 17	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2	c.421-25G>A		intron_variant	Intron 4 of 17		XP_005249033.1
CD2AP	XM_011514449.3	c.274-25G>A		intron_variant	Intron 3 of 16		XP_011512751.1
CD2AP	XM_017010641.2	c.421-25G>A		intron_variant	Intron 4 of 13		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5	c.421-25G>A		intron_variant	Intron 4 of 17	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91604 AN: 151846 Hom.: 28433 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.628

GnomAD2 exomes AF: 0.606 AC: 151993 AN: 250642 AF XY: 0.620

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.702

Gnomad EAS exome AF: 0.288

Gnomad FIN exome AF: 0.590

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.647

GnomAD4 exome AF: 0.662 AC: 965671 AN: 1458870 Hom.: 324628 Cov.: 35 AF XY: 0.664 AC XY: 481604 AN XY: 725738

African (AFR) AF: 0.528 AC: 17637 AN: 33382

American (AMR) AF: 0.474 AC: 21152 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 18275 AN: 26080

East Asian (EAS) AF: 0.300 AC: 11864 AN: 39588

South Asian (SAS) AF: 0.667 AC: 57379 AN: 86000

European-Finnish (FIN) AF: 0.598 AC: 31937 AN: 53364

Middle Eastern (MID) AF: 0.698 AC: 4014 AN: 5748

European-Non Finnish (NFE) AF: 0.689 AC: 764480 AN: 1109870

Other (OTH) AF: 0.646 AC: 38933 AN: 60254

GnomAD4 genome AF: 0.603 AC: 91656 AN: 151964 Hom.: 28445 Cov.: 32 AF XY: 0.594 AC XY: 44145 AN XY: 74292

African (AFR) AF: 0.528 AC: 21875 AN: 41422

American (AMR) AF: 0.515 AC: 7861 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2423 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5172

South Asian (SAS) AF: 0.648 AC: 3121 AN: 4814

European-Finnish (FIN) AF: 0.583 AC: 6147 AN: 10552

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46600 AN: 67974

Other (OTH) AF: 0.628 AC: 1316 AN: 2096

Alfa AF: 0.599 Hom.: 3787

Bravo AF: 0.593

Asia WGS AF: 0.476 AC: 1654 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 69. Only high quality variants are reported. -

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.58
PhyloP100		-0.32
Mutation Taster		=5/95	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs9473132; hg19: chr6-47522357; COSMIC: COSV63761683;