dbSNP rs185609509: CD2AP:c.1417+19C>T (chr6-47599462-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012120.3(CD2AP):c.1417+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,604,408 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

CD2AP
NM_012120.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.490

Publications

0 publications found

Variant links:

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: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
inherited focal segmental glomerulosclerosis
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CD2AP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-47599462-C-T is Benign according to our data. Variant chr6-47599462-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

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.1417+19C>T		intron	N/A	NP_036252.1	Q9Y5K6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.1417+19C>T	intron	N/A	ENSP00000352264.5	Q9Y5K6
CD2AP	ENST00000865253.1		c.1420+19C>T	intron	N/A	ENSP00000535312.1
CD2AP	ENST00000931707.1		c.1408+19C>T	intron	N/A	ENSP00000601766.1

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.000359

AC:

AN:

245282

AF XY:

0.000377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00773

Gnomad EAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.000191

AC:

277

AN:

1453296

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

144

AN XY:

723088

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33068

American (AMR)

AF:

0.00

AC:

AN:

44324

Ashkenazi Jewish (ASJ)

AF:

0.00786

AC:

204

AN:

25954

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39298

South Asian (SAS)

AF:

0.0000351

AC:

AN:

85440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000380

AC:

AN:

1106244

Other (OTH)

AF:

0.000417

AC:

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000152

AC:

AN:

151112

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73732

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41116

American (AMR)

AF:

0.0000660

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3464

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67808

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.000189

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Focal segmental glomerulosclerosis 3, susceptibility to (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

(source)

DANN

Benign

0.43

PhyloP100

0.49

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over