Variant chr16-82090913-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002153.3(HSD17B2):c.676A>G(p.Met226Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00876 in 1,611,502 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 86 hom. )

Consequence

HSD17B2
NM_002153.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.270

Variant links:

Genes affected

HSD17B2 (HGNC:5211): (hydroxysteroid 17-beta dehydrogenase 2) Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in response to retinoic acid. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B2 links:

HSD17B2-AS1 (HGNC:56281): (HSD17B2 antisense RNA 1)

HSD17B2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005282551).

BP6

Variant 16-82090913-A-G is Benign according to our data. Variant chr16-82090913-A-G is described in ClinVar as [Benign]. Clinvar id is 787563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3 linkuse as main transcript	c.676A>G	p.Met226Val	missense_variant	4/5	ENST00000199936.9	NP_002144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HSD17B2	ENST00000199936.9 linkuse as main transcript	c.676A>G	p.Met226Val	missense_variant	4/5	1	NM_002153.3	ENSP00000199936	P1
HSD17B2-AS1	ENST00000567021.1 linkuse as main transcript	n.44-19724T>C		intron_variant, non_coding_transcript_variant		5
HSD17B2	ENST00000568090.5 linkuse as main transcript	c.268A>G	p.Met90Val	missense_variant	4/5	3		ENSP00000456529
HSD17B2	ENST00000566838.2 linkuse as main transcript	c.304A>G	p.Met102Val	missense_variant	3/3	2		ENSP00000456471

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1149

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00742

AC:

1848

AN:

249088

Hom.:

AF XY:

0.00779

AC XY:

1048

AN XY:

134582

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.00533

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00778

GnomAD4 exome

AF:

0.00889

AC:

12974

AN:

1459238

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

6456

AN XY:

725722

show subpopulations

Gnomad4 AFR exome

AF:

0.00150

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00480

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00672

GnomAD4 genome

AF:

0.00754

AC:

1148

AN:

152264

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

555

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00960

Hom.:

Bravo

AF:

0.00571

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00783

AC:

950

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.00861

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.053

DANN

Benign

0.68

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.35

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.099

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.027

B;.;.

Vest4

0.29

MVP

0.56

MPC

0.0062

ClinPred

0.0017

GERP RS

-0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.50

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