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GeneBe

rs370143870

chr6-47478264-G-Achr6-47478264-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_012120.3(CD2AP):c.4+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,568,450 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 11 hom. )

Consequence

CD2AP
NM_012120.3 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.754
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-47478264-G-A is Benign according to our data. Variant chr6-47478264-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00188 (286/152262) while in subpopulation NFE AF= 0.00353 (240/68008). AF 95% confidence interval is 0.00316. There are 0 homozygotes in gnomad4. There are 124 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD2APNM_012120.3 linkuse as main transcriptc.4+16G>A intron_variant ENST00000359314.5
CD2APXM_005248976.2 linkuse as main transcriptc.4+16G>A intron_variant
CD2APXM_017010641.2 linkuse as main transcriptc.4+16G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD2APENST00000359314.5 linkuse as main transcriptc.4+16G>A intron_variant 1 NM_012120.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00189
AC:
287
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000772
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00354
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00136
AC:
230
AN:
169264
Hom.:
0
AF XY:
0.00132
AC XY:
121
AN XY:
91622
show subpopulations
Gnomad AFR exome
AF:
0.000905
Gnomad AMR exome
AF:
0.000412
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000416
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00298
Gnomad OTH exome
AF:
0.00174
GnomAD4 exome
AF:
0.00335
AC:
4741
AN:
1416188
Hom.:
11
Cov.:
35
AF XY:
0.00323
AC XY:
2264
AN XY:
700276
show subpopulations
Gnomad4 AFR exome
AF:
0.000493
Gnomad4 AMR exome
AF:
0.000606
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000372
Gnomad4 FIN exome
AF:
0.000204
Gnomad4 NFE exome
AF:
0.00413
Gnomad4 OTH exome
AF:
0.00313
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00188
AC:
286
AN:
152262
Hom.:
0
Cov.:
32
AF XY:
0.00167
AC XY:
124
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000770
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00353
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00104
Hom.:
0
Bravo
AF:
0.00193

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 02, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
9.8
Dann
Benign
0.93
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370143870; hg19: chr6-47446000; API