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rs140627775

chr6-47574218-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012120.3(CD2AP):c.696C>T(p.Ser232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,852 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 12 hom., cov: 32)
Exomes 𝑓: 0.011 ( 126 hom. )

Consequence

CD2AP
NM_012120.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.289
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 -19 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=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-47574218-C-T is Benign according to our data. Variant chr6-47574218-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-47574218-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.289 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00895 (1363/152222) while in subpopulation AMR AF= 0.0145 (222/15290). AF 95% confidence interval is 0.013. There are 12 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD2APNM_012120.3 linkuse as main transcriptc.696C>T p.Ser232= synonymous_variant 6/18 ENST00000359314.5
CD2APXM_005248976.2 linkuse as main transcriptc.696C>T p.Ser232= synonymous_variant 6/18
CD2APXM_011514449.3 linkuse as main transcriptc.549C>T p.Ser183= synonymous_variant 5/17
CD2APXM_017010641.2 linkuse as main transcriptc.696C>T p.Ser232= synonymous_variant 6/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD2APENST00000359314.5 linkuse as main transcriptc.696C>T p.Ser232= synonymous_variant 6/181 NM_012120.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00897
AC:
1364
AN:
152106
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00534
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0145
Gnomad ASJ
AF:
0.0167
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00808
Gnomad FIN
AF:
0.00264
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0110
Gnomad OTH
AF:
0.0167
GnomAD3 exomes
AF:
0.00935
AC:
2349
AN:
251250
Hom.:
22
AF XY:
0.00998
AC XY:
1355
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00548
Gnomad AMR exome
AF:
0.0100
Gnomad ASJ exome
AF:
0.0169
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00849
Gnomad FIN exome
AF:
0.00231
Gnomad NFE exome
AF:
0.0119
Gnomad OTH exome
AF:
0.0137
GnomAD4 exome
AF:
0.0106
AC:
15425
AN:
1461630
Hom.:
126
Cov.:
31
AF XY:
0.0106
AC XY:
7689
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00615
Gnomad4 AMR exome
AF:
0.0106
Gnomad4 ASJ exome
AF:
0.0162
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00903
Gnomad4 FIN exome
AF:
0.00247
Gnomad4 NFE exome
AF:
0.0113
Gnomad4 OTH exome
AF:
0.0117
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00895
AC:
1363
AN:
152222
Hom.:
12
Cov.:
32
AF XY:
0.00868
AC XY:
646
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00532
Gnomad4 AMR
AF:
0.0145
Gnomad4 ASJ
AF:
0.0167
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00809
Gnomad4 FIN
AF:
0.00264
Gnomad4 NFE
AF:
0.0110
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.0106
Hom.:
6
Bravo
AF:
0.0106
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0150
EpiControl
AF:
0.0165

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 13, 2020- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Focal segmental glomerulosclerosis 3, susceptibility to Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
Focal segmental glomerulosclerosis Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenSep 06, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
7.5
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs140627775; hg19: chr6-47541954; API