Genetic Variant CSDC2:p.Glu30Lys (chr22-41572053-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014460.4(CSDC2):c.88G>A(p.Glu30Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,362,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CSDC2
NM_014460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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]

CSDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08073613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSDC2	NM_014460.4 link	c.88G>A	p.Glu30Lys	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
CSDC2	ENST00000306149.12 link	c.88G>A	p.Glu30Lys	missense_variant	Exon 2 of 4	1	NM_014460.4	ENSP00000302485.7		Q9Y534
CSDC2	ENST00000460790.1 link	c.37G>A	p.Glu13Lys	missense_variant	Exon 1 of 3	3		ENSP00000417127.1		H7C4E7

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

44320

Hom.:

AF XY:

0.0000933

AC XY:

AN XY:

21434

show subpopulations

Gnomad AFR exome

AF:

0.000448

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000455

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1210516

Hom.:

Cov.:

AF XY:

0.0000462

AC XY:

AN XY:

584600

show subpopulations

Gnomad4 AFR exome

AF:

0.000767

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000233

Gnomad4 OTH exome

AF:

0.000163

GnomAD4 genome

AF:

0.000289

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000242

ExAC

AF:

0.0000435

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88G>A (p.E30K) 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 88, causing the glutamic acid (E) at amino acid position 30 to be replaced by a lysine (K). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-0.020

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

L;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.16

T;T

Polyphen

0.0030

B;.

Vest4

0.54

MVP

0.50

MPC

0.55

ClinPred

0.14

GERP RS

4.0

Varity_R

0.20

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over