Genetic Variant DHRS2:p.Gln81Glu (chr14-23639279-C-G) – 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_005794.4(DHRS2):c.241C>G(p.Gln81Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000646 in 1,609,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

DHRS2
NM_005794.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266

Publications

0 publications found

Variant links:

Genes affected

DHRS2 (HGNC:18349): (dehydrogenase/reductase 2) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members of this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. Alternative promoter use and alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

DHRS2 links:

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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=0.039880276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005794.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS2	NM_005794.4	MANE Select	c.241C>G	p.Gln81Glu	missense	Exon 3 of 9	NP_005785.1	Q13268-1
DHRS2	NM_182908.5		c.241C>G	p.Gln81Glu	missense	Exon 3 of 9	NP_878912.1	Q13268-2
DHRS2	NM_001318835.1		c.241C>G	p.Gln81Glu	missense	Exon 3 of 5	NP_001305764.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS2	ENST00000250383.11	TSL:1 MANE Select	c.241C>G	p.Gln81Glu	missense	Exon 3 of 9	ENSP00000250383.7	Q13268-1
DHRS2	ENST00000344777.11	TSL:1	c.241C>G	p.Gln81Glu	missense	Exon 3 of 9	ENSP00000344674.7	Q13268-2
DHRS2	ENST00000553896.5	TSL:1	n.400C>G		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

245434

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000652

AC:

AN:

1457656

Hom.:

Cov.:

AF XY:

0.0000662

AC XY:

AN XY:

724970

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33380

American (AMR)

AF:

0.0000906

AC:

AN:

44168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25794

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000187

AC:

AN:

85482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53196

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

1109990

Other (OTH)

AF:

0.0000996

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000114

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000157

AC:

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

0.089

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.1

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.27

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

M_CAP

Benign

0.0051

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.015

PhyloP100

0.27

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.9

REVEL

Benign

0.038

Sift

Benign

0.038

Sift4G

Benign

0.34

Polyphen

0.014

Vest4

0.22

MVP

0.076

MPC

0.022

ClinPred

0.021

GERP RS

-0.81

PromoterAI

0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.31

Mutation Taster

=98/2

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