Genetic Variant CSDC2:p.Thr6Met (chr22-41571982-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014460.4(CSDC2):c.17C>T(p.Thr6Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,357,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

CSDC2
NM_014460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1278756).

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.17C>T	p.Thr6Met	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.17C>T	p.Thr6Met	missense	Exon 2 of 4	ENSP00000302485.7	Q9Y534
CSDC2	ENST00000901851.1		c.17C>T	p.Thr6Met	missense	Exon 3 of 5	ENSP00000571910.1
CSDC2	ENST00000901852.1		c.17C>T	p.Thr6Met	missense	Exon 2 of 4	ENSP00000571911.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

31082

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000581

AC:

AN:

1205118

Hom.:

Cov.:

AF XY:

0.00000686

AC XY:

AN XY:

582752

show subpopulations

African (AFR)

AF:

0.000167

AC:

AN:

24014

American (AMR)

AF:

0.00

AC:

AN:

9692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16786

East Asian (EAS)

AF:

0.0000363

AC:

AN:

27584

South Asian (SAS)

AF:

0.00

AC:

AN:

44620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

984880

Other (OTH)

AF:

0.00

AC:

AN:

48886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

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:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41442

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000987

Hom.:

Bravo

AF:

0.0000831

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

0.10

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.79

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.6

PhyloP100

4.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.56

REVEL

Benign

0.037

Sift

Benign

0.036

Sift4G

Benign

0.10

Polyphen

0.20

Vest4

0.23

MVP

0.39

MPC

0.54

ClinPred

0.30

GERP RS

4.0

PromoterAI

-0.056

Neutral

(source)

Varity_R

0.053

gMVP

0.26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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