dbSNP rs886061511: CD2AP:c.-329C>T (chr6-47477916-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012120.3(CD2AP):c.-329C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 462,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CD2AP
NM_012120.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.124

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 links:

CD2AP-DT (HGNC:55263): (CD2AP divergent transcript)

CD2AP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD2AP	NM_012120.3	MANE Select	c.-329C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_036252.1	Q9Y5K6
CD2AP	NM_012120.3	MANE Select	c.-329C>T	5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
CD2AP-DT	NR_187257.1		n.157G>A	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.-329C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.-329C>T	5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
CD2AP	ENST00000931707.1		c.-329C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000601766.1

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

150382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000961

AC:

AN:

312068

Hom.:

Cov.:

AF XY:

0.0000122

AC XY:

AN XY:

163960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6232

American (AMR)

AF:

0.00

AC:

AN:

11244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9594

East Asian (EAS)

AF:

0.00

AC:

AN:

18066

South Asian (SAS)

AF:

0.00

AC:

AN:

35892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1404

European-Non Finnish (NFE)

AF:

0.0000105

AC:

AN:

191094

Other (OTH)

AF:

0.0000536

AC:

AN:

18652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000113

AC:

AN:

150382

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

73408

show subpopulations

African (AFR)

AF:

0.000267

AC:

AN:

41176

American (AMR)

AF:

0.000263

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5004

South Asian (SAS)

AF:

0.00

AC:

AN:

4674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67504

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Focal segmental glomerulosclerosis 3, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.0

(source)

DANN

Benign

0.80

PhyloP100

0.12

PromoterAI

-0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over