Genetic Variant HSD17B2:c.664+724G>C (chr16-82071851-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002153.3(HSD17B2):c.664+724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 153,688 control chromosomes in the GnomAD database, including 81 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 0.028 ( 79 hom., cov: 33)

Exomes 𝑓: 0.043 ( 2 hom. )

Consequence

HSD17B2
NM_002153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.613

Publications

0 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=-0.85).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0284 (4332/152282) while in subpopulation NFE AF = 0.042 (2859/68012). AF 95% confidence interval is 0.0408. There are 79 homozygotes in GnomAd4. There are 2033 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 79 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.664+724G>C		intron	N/A	NP_002144.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.664+724G>C	intron	N/A	ENSP00000199936.4
HSD17B2	ENST00000569351.2	TSL:2	c.*569G>C	3_prime_UTR	Exon 3 of 3	ENSP00000454931.1
HSD17B2	ENST00000568090.5	TSL:3	c.256+724G>C	intron	N/A	ENSP00000456529.1

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4335

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00799

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0421

Gnomad OTH

AF:

0.0411

GnomAD4 exome

AF:

0.0427

AC:

AN:

1406

Hom.:

Cov.:

AF XY:

0.0440

AC XY:

AN XY:

750

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.0261

AC:

AN:

230

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0478

AC:

AN:

1026

Other (OTH)

AF:

0.0455

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0284

AC:

4332

AN:

152282

Hom.:

Cov.:

AF XY:

0.0273

AC XY:

2033

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00799

AC:

332

AN:

41560

American (AMR)

AF:

0.0262

AC:

401

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0827

AC:

287

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.0116

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0228

AC:

242

AN:

10616

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2859

AN:

68012

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

218

436

655

873

1091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0114

Hom.:

Bravo

AF:

0.0279

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.40

(source)

DANN

Benign

0.75

PhyloP100

-0.61

Mutation Taster

=100/0

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

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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