Genetic Variant NM_014460.4:c.128G>A (chr22-41572093-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43W) has been classified 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04830876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDC2	NM_014460.4	MANE Select	c.128G>A	p.Arg43Gln	missense	Exon 2 of 4	NP_055275.1	Q9Y534

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSDC2	ENST00000306149.12	TSL:1 MANE Select	c.128G>A	p.Arg43Gln	missense	Exon 2 of 4	ENSP00000302485.7	Q9Y534
CSDC2	ENST00000901851.1		c.128G>A	p.Arg43Gln	missense	Exon 3 of 5	ENSP00000571910.1
CSDC2	ENST00000901852.1		c.128G>A	p.Arg43Gln	missense	Exon 2 of 4	ENSP00000571911.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151924

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000633

AC:

AN:

79008

AF XY:

0.0000485

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000794

GnomAD4 exome

AF:

0.0000448

AC:

AN:

1206298

Hom.:

Cov.:

AF XY:

0.0000447

AC XY:

AN XY:

581612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25170

American (AMR)

AF:

0.00

AC:

AN:

12950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16206

East Asian (EAS)

AF:

0.000336

AC:

AN:

29806

South Asian (SAS)

AF:

0.00

AC:

AN:

41518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44146

Middle Eastern (MID)

AF:

0.000208

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.00000916

AC:

AN:

983028

Other (OTH)

AF:

0.000699

AC:

AN:

48670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41494

American (AMR)

AF:

0.000392

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000976

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67928

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000525

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.0063

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.029

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0049

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

PhyloP100

9.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.68

REVEL

Benign

0.16

Sift

Benign

0.089

Sift4G

Benign

0.11

Polyphen

0.55

Vest4

0.40

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0166)

MVP

0.57

MPC

0.64

ClinPred

0.15

GERP RS

4.9

PromoterAI

-0.0060

Neutral

(source)

Varity_R

0.12

gMVP

0.23

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over