22-41572093-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014460.4(CSDC2):​c.128G>A​(p.Arg43Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,358,340 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

CSDC2
NM_014460.4 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
Variant links:
Genes affected
CSDC2 (HGNC:30359): (cold shock domain containing C2) Predicted to enable mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04830876).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSDC2NM_014460.4 linkc.128G>A p.Arg43Gln missense_variant Exon 2 of 4 ENST00000306149.12 NP_055275.1 Q9Y534

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSDC2ENST00000306149.12 linkc.128G>A p.Arg43Gln missense_variant Exon 2 of 4 1 NM_014460.4 ENSP00000302485.7 Q9Y534
CSDC2ENST00000460790.1 linkc.77G>A p.Arg26Gln missense_variant Exon 1 of 3 3 ENSP00000417127.1 H7C4E7

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
151924
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000974
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.0000633
AC:
5
AN:
79008
Hom.:
0
AF XY:
0.0000485
AC XY:
2
AN XY:
41212
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000755
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000794
GnomAD4 exome
AF:
0.0000448
AC:
54
AN:
1206298
Hom.:
0
Cov.:
32
AF XY:
0.0000447
AC XY:
26
AN XY:
581612
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000336
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000916
Gnomad4 OTH exome
AF:
0.000699
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152042
Hom.:
1
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000976
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000113
ExAC
AF:
0.0000525
AC:
6
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.128G>A (p.R43Q) alteration is located in exon 2 (coding exon 1) of the CSDC2 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the arginine (R) at amino acid position 43 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.0063
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.029
T;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.048
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.5
L;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.16
Sift
Benign
0.089
T;D
Sift4G
Benign
0.11
T;T
Polyphen
0.55
P;.
Vest4
0.40
MutPred
0.23
Gain of relative solvent accessibility (P = 0.0166);.;
MVP
0.57
MPC
0.64
ClinPred
0.15
T
GERP RS
4.9
Varity_R
0.12
gMVP
0.23

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: rs374172494; hg19: chr22-41968097; API