6-47595956-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012120.3(CD2AP):c.1204C>T(p.Leu402Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,612,860 control chromosomes in the GnomAD database, including 801,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73392 hom., cov: 30)

Exomes 𝑓: 1.0 ( 727695 hom. )

Consequence

CD2AP
NM_012120.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.222

Publications

19 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-47595956-C-T is Benign according to our data. Variant chr6-47595956-C-T is described in ClinVar as Benign. ClinVar VariationId is 260181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.222 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CD2AP	NM_012120.3 link	c.1204C>T	p.Leu402Leu	synonymous_variant	Exon 12 of 18	ENST00000359314.5	NP_036252.1
CD2AP	XM_005248976.2 link	c.1192C>T	p.Leu398Leu	synonymous_variant	Exon 12 of 18		XP_005249033.1
CD2AP	XM_011514449.3 link	c.1057C>T	p.Leu353Leu	synonymous_variant	Exon 11 of 17		XP_011512751.1
CD2AP	XM_017010641.2 link	c.1204C>T	p.Leu402Leu	synonymous_variant	Exon 12 of 14		XP_016866130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2AP	ENST00000359314.5 link	c.1204C>T	p.Leu402Leu	synonymous_variant	Exon 12 of 18	1	NM_012120.3	ENSP00000352264.5

Frequencies

GnomAD3 genomes

AF:

0.982

AC:

149241

AN:

152010

Hom.:

73335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.936

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.991

GnomAD2 exomes

AF:

0.995

AC:

250173

AN:

251418

AF XY:

0.996

show subpopulations

Gnomad AFR exome

AF:

0.932

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.998

AC:

1457979

AN:

1460732

Hom.:

727695

Cov.:

AF XY:

0.998

AC XY:

725563

AN XY:

726760

show subpopulations

African (AFR)

AF:

0.931

AC:

31127

AN:

33416

American (AMR)

AF:

0.997

AC:

44565

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26098

AN:

26098

East Asian (EAS)

AF:

1.00

AC:

39664

AN:

39664

South Asian (SAS)

AF:

1.00

AC:

86203

AN:

86210

European-Finnish (FIN)

AF:

1.00

AC:

53414

AN:

53414

Middle Eastern (MID)

AF:

0.996

AC:

5740

AN:

5762

European-Non Finnish (NFE)

AF:

1.00

AC:

1111049

AN:

1111136

Other (OTH)

AF:

0.996

AC:

60119

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.982

AC:

149358

AN:

152128

Hom.:

73392

Cov.:

AF XY:

0.983

AC XY:

73074

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.937

AC:

38872

AN:

41502

American (AMR)

AF:

0.993

AC:

15161

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3468

AN:

3468

East Asian (EAS)

AF:

1.00

AC:

5150

AN:

5150

South Asian (SAS)

AF:

1.00

AC:

4804

AN:

4806

European-Finnish (FIN)

AF:

1.00

AC:

10614

AN:

10614

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

67992

AN:

68004

Other (OTH)

AF:

0.991

AC:

2091

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

248

371

495

619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.992

Hom.:

53739

Bravo

AF:

0.979

Asia WGS

AF:

0.997

AC:

3465

AN:

3476

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 100% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 93. Only high quality variants are reported. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 3, susceptibility to

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 20, 2019

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

-0.65

CADD

Benign

3.0

(source)

DANN

Benign

0.64

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(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