Genetic Variant NM_012120.3:c.-267G>A (chr6-47477978-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012120.3(CD2AP):c.-267G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 561,740 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 10 hom. )

Consequence

CD2AP
NM_012120.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.471

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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-47477978-G-A is Benign according to our data. Variant chr6-47477978-G-A is described in ClinVar as Benign. ClinVar VariationId is 357155.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000815 (124/152074) while in subpopulation SAS AF = 0.00974 (47/4824). AF 95% confidence interval is 0.00753. There are 0 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 10 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.-267G>A		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.95C>T		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.-267G>A	5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
CD2AP	ENST00000931707.1		c.-267G>A	5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
CD2AP	ENST00000931708.1		c.-267G>A	5_prime_UTR	Exon 1 of 18	ENSP00000601767.1

Frequencies

GnomAD3 genomes

AF:

0.000823

AC:

125

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00994

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.00240

GnomAD4 exome

AF:

0.00170

AC:

698

AN:

409666

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

517

AN XY:

216032

show subpopulations

African (AFR)

AF:

0.000219

AC:

AN:

9130

American (AMR)

AF:

0.000488

AC:

AN:

16410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12312

East Asian (EAS)

AF:

0.0000372

AC:

AN:

26858

South Asian (SAS)

AF:

0.0113

AC:

486

AN:

43114

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

27358

Middle Eastern (MID)

AF:

0.00386

AC:

AN:

1814

European-Non Finnish (NFE)

AF:

0.000679

AC:

169

AN:

248778

Other (OTH)

AF:

0.000921

AC:

AN:

23892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

104

138

173

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:

0.000815

AC:

124

AN:

152074

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41534

American (AMR)

AF:

0.000850

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5150

South Asian (SAS)

AF:

0.00974

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000948

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000692

AC:

AN:

67940

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.000318

Hom.:

Bravo

AF:

0.000635

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

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

-0.84

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.47

PromoterAI

-0.0047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=299/1

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

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