Genetic Variant HSD17B2:c.803-102C>G (chr16-82097973-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.803-102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,057,096 control chromosomes in the GnomAD database, including 442,650 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 0.84 ( 54747 hom., cov: 30)

Exomes 𝑓: 0.92 ( 387903 hom. )

Consequence

HSD17B2
NM_002153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

Publications

7 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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. 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
	HSD17B2	NM_002153.3	MANE Select	c.803-102C>G		intron	N/A	NP_002144.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.803-102C>G	intron	N/A	ENSP00000199936.4
HSD17B2	ENST00000566838.2	TSL:2	c.*6797C>G	3_prime_UTR	Exon 3 of 3	ENSP00000456471.1
HSD17B2	ENST00000891334.1		c.803-102C>G	intron	N/A	ENSP00000561393.1

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

127126

AN:

151582

Hom.:

54723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.971

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.853

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.953

Gnomad OTH

AF:

0.867

GnomAD4 exome

AF:

0.921

AC:

834191

AN:

905396

Hom.:

387903

Cov.:

AF XY:

0.922

AC XY:

418873

AN XY:

454524

show subpopulations

African (AFR)

AF:

0.644

AC:

13183

AN:

20476

American (AMR)

AF:

0.657

AC:

13824

AN:

21048

Ashkenazi Jewish (ASJ)

AF:

0.941

AC:

15063

AN:

16014

East Asian (EAS)

AF:

0.655

AC:

21663

AN:

33050

South Asian (SAS)

AF:

0.862

AC:

38453

AN:

44630

European-Finnish (FIN)

AF:

0.931

AC:

42148

AN:

45252

Middle Eastern (MID)

AF:

0.913

AC:

2546

AN:

2790

European-Non Finnish (NFE)

AF:

0.955

AC:

651308

AN:

682240

Other (OTH)

AF:

0.902

AC:

36003

AN:

39896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

2733

5466

8199

10932

13665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11840

23680

35520

47360

59200

<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:

0.838

AC:

127193

AN:

151700

Hom.:

54747

Cov.:

AF XY:

0.834

AC XY:

61842

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.667

AC:

27530

AN:

41276

American (AMR)

AF:

0.738

AC:

11228

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.950

AC:

3295

AN:

3468

East Asian (EAS)

AF:

0.668

AC:

3441

AN:

5154

South Asian (SAS)

AF:

0.854

AC:

4108

AN:

4808

European-Finnish (FIN)

AF:

0.938

AC:

9866

AN:

10518

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.953

AC:

64740

AN:

67932

Other (OTH)

AF:

0.865

AC:

1830

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

884

1767

2651

3534

4418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.873

Hom.:

3044

Bravo

AF:

0.816

Asia WGS

AF:

0.760

AC:

2638

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.12

(source)

DANN

Benign

0.36

PhyloP100

-0.039

Mutation Taster

=100/0

polymorphism (auto)

(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

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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