Genetic Variant HSD17B2:c.802+2186C>G (chr16-82093225-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002153.3(HSD17B2):c.802+2186C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,062 control chromosomes in the GnomAD database, including 25,042 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25040 hom., cov: 32)

Exomes 𝑓: 0.60 ( 2 hom. )

Consequence

HSD17B2
NM_002153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.185

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3 link	c.802+2186C>G		intron_variant	Intron 4 of 4	ENST00000199936.9	NP_002144.1	P37059

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD17B2	ENST00000199936.9 link	c.802+2186C>G	intron_variant	Intron 4 of 4	1	NM_002153.3	ENSP00000199936.4	P37059
HSD17B2	ENST00000566838.2 link	c.*2049C>G	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000456471.1	H3BRZ6
HSD17B2	ENST00000568090.5 link	c.394+2186C>G	intron_variant	Intron 4 of 4	3		ENSP00000456529.1	H3BS44
HSD17B2-AS1	ENST00000567021.2 link	n.44-22036G>C	intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86801

AN:

151934

Hom.:

25029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.595

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.571

AC:

86834

AN:

152052

Hom.:

25040

Cov.:

AF XY:

0.566

AC XY:

42053

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.521

AC:

21595

AN:

41454

American (AMR)

AF:

0.510

AC:

7794

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2399

AN:

3466

East Asian (EAS)

AF:

0.561

AC:

2907

AN:

5178

South Asian (SAS)

AF:

0.469

AC:

2256

AN:

4810

European-Finnish (FIN)

AF:

0.566

AC:

5985

AN:

10566

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41900

AN:

67974

Other (OTH)

AF:

0.589

AC:

1245

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1926

3852

5778

7704

9630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.460

Hom.:

1241

Bravo

AF:

0.567

Asia WGS

AF:

0.471

AC:

1637

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

(source)

DANN

Benign

0.65

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over