rs719856

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012120.3(CD2AP):​c.*2759G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,980 control chromosomes in the GnomAD database, including 5,505 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5489 hom., cov: 32)
Exomes 𝑓: 0.32 ( 16 hom. )

Consequence

CD2AP
NM_012120.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0960

Publications

10 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD2APNM_012120.3 linkc.*2759G>A 3_prime_UTR_variant Exon 18 of 18 ENST00000359314.5 NP_036252.1 Q9Y5K6
CD2APXM_005248976.2 linkc.*2759G>A 3_prime_UTR_variant Exon 18 of 18 XP_005249033.1
CD2APXM_011514449.3 linkc.*2759G>A 3_prime_UTR_variant Exon 17 of 17 XP_011512751.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD2APENST00000359314.5 linkc.*2759G>A 3_prime_UTR_variant Exon 18 of 18 1 NM_012120.3 ENSP00000352264.5 Q9Y5K6

Frequencies

GnomAD3 genomes
AF:
0.251
AC:
37987
AN:
151428
Hom.:
5479
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.183
Gnomad AMI
AF:
0.311
Gnomad AMR
AF:
0.374
Gnomad ASJ
AF:
0.155
Gnomad EAS
AF:
0.602
Gnomad SAS
AF:
0.219
Gnomad FIN
AF:
0.328
Gnomad MID
AF:
0.188
Gnomad NFE
AF:
0.233
Gnomad OTH
AF:
0.233
GnomAD4 exome
AF:
0.317
AC:
137
AN:
432
Hom.:
16
Cov.:
0
AF XY:
0.304
AC XY:
79
AN XY:
260
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.317
AC:
135
AN:
426
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.500
AC:
1
AN:
2
Other (OTH)
AF:
0.250
AC:
1
AN:
4
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
6
12
18
24
30
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.251
AC:
38016
AN:
151548
Hom.:
5489
Cov.:
32
AF XY:
0.260
AC XY:
19288
AN XY:
74050
show subpopulations
African (AFR)
AF:
0.183
AC:
7565
AN:
41340
American (AMR)
AF:
0.375
AC:
5715
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.155
AC:
538
AN:
3464
East Asian (EAS)
AF:
0.601
AC:
3107
AN:
5166
South Asian (SAS)
AF:
0.219
AC:
1052
AN:
4798
European-Finnish (FIN)
AF:
0.328
AC:
3437
AN:
10466
Middle Eastern (MID)
AF:
0.171
AC:
50
AN:
292
European-Non Finnish (NFE)
AF:
0.233
AC:
15780
AN:
67762
Other (OTH)
AF:
0.232
AC:
488
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1386
2772
4157
5543
6929
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
392
784
1176
1568
1960
<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:
0.236
Hom.:
2562
Bravo
AF:
0.255
Asia WGS
AF:
0.397
AC:
1374
AN:
3464

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Focal segmental glomerulosclerosis 3, susceptibility to Benign:1
Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.9
DANN
Benign
0.47
PhyloP100
0.096
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs719856; hg19: chr6-47594722; API