rs140627775

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012120.3(CD2AP):c.696C>T(p.Ser232Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,852 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 12 hom., cov: 32)

Exomes 𝑓: 0.011 ( 126 hom. )

Consequence

CD2AP
NM_012120.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.289

Publications

3 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: 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

CD2AP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 6-47574218-C-T is Benign according to our data. Variant chr6-47574218-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.289 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00895 (1363/152222) while in subpopulation AMR AF = 0.0145 (222/15290). AF 95% confidence interval is 0.013. There are 12 homozygotes in GnomAd4. There are 646 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2AP	NM_012120.3 link	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 6 of 18	ENST00000359314.5	NP_036252.1	Q9Y5K6
CD2AP	XM_005248976.2 link	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 6 of 18		XP_005249033.1
CD2AP	XM_011514449.3 link	c.549C>T	p.Ser183Ser	synonymous_variant	Exon 5 of 17		XP_011512751.1
CD2AP	XM_017010641.2 link	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 6 of 14		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5 link	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 6 of 18	1	NM_012120.3	ENSP00000352264.5		Q9Y5K6

Frequencies

GnomAD3 genomes

AF:

0.00897

AC:

1364

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00534

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00935

AC:

2349

AN:

251250

AF XY:

0.00998

show subpopulations

Gnomad AFR exome

AF:

0.00548

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0106

AC:

15425

AN:

1461630

Hom.:

126

Cov.:

AF XY:

0.0106

AC XY:

7689

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00615

AC:

206

AN:

33472

American (AMR)

AF:

0.0106

AC:

474

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

423

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00903

AC:

779

AN:

86234

European-Finnish (FIN)

AF:

0.00247

AC:

132

AN:

53404

Middle Eastern (MID)

AF:

0.0324

AC:

187

AN:

5766

European-Non Finnish (NFE)

AF:

0.0113

AC:

12519

AN:

1111872

Other (OTH)

AF:

0.0117

AC:

705

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

735

1471

2206

2942

3677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.00895

AC:

1363

AN:

152222

Hom.:

Cov.:

AF XY:

0.00868

AC XY:

646

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00532

AC:

221

AN:

41514

American (AMR)

AF:

0.0145

AC:

222

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00809

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

749

AN:

68010

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

147

220

294

367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0106

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0165

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 13, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 3, susceptibility to

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Focal segmental glomerulosclerosis

Benign:1

Sep 06, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely 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

-0.36

CADD

Benign

7.5

(source)

DANN

Benign

0.65

PhyloP100

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over