Genetic Variant DHRS2:p.Cys92Cys (chr14-23639314-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005794.4(DHRS2):c.276C>T(p.Cys92Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,589,976 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

DHRS2
NM_005794.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.334

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 14-23639314-C-T is Benign according to our data. Variant chr14-23639314-C-T is described in ClinVar as [Benign]. Clinvar id is 777240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.334 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS2	NM_005794.4 link	c.276C>T	p.Cys92Cys	synonymous_variant	Exon 3 of 9	ENST00000250383.11	NP_005785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS2	ENST00000250383.11 link	c.276C>T	p.Cys92Cys	synonymous_variant	Exon 3 of 9	1	NM_005794.4	ENSP00000250383.7		Q13268-1

Frequencies

GnomAD3 genomes

AF:

0.00852

AC:

1297

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00881

AC:

1984

AN:

225264

Hom.:

AF XY:

0.00910

AC XY:

1102

AN XY:

121132

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00585

Gnomad ASJ exome

AF:

0.00873

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00373

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00958

GnomAD4 exome

AF:

0.0114

AC:

16391

AN:

1437716

Hom.:

118

Cov.:

AF XY:

0.0113

AC XY:

8034

AN XY:

713384

show subpopulations

Gnomad4 AFR exome

AF:

0.00207

Gnomad4 AMR exome

AF:

0.00579

Gnomad4 ASJ exome

AF:

0.00973

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00362

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00851

AC:

1295

AN:

152260

Hom.:

Cov.:

AF XY:

0.00809

AC XY:

602

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00793

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.4

DANN

Benign

0.84

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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.

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