Genetic Variant NM_002153.3:c.802+355T>C (chr16-82091394-T-C) – 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+355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 314,232 control chromosomes in the GnomAD database, including 345 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 0.036 ( 153 hom., cov: 32)

Exomes 𝑓: 0.038 ( 192 hom. )

Consequence

HSD17B2
NM_002153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

1 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=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0564 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.802+355T>C		intron	N/A	NP_002144.1	P37059

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.802+355T>C	intron	N/A	ENSP00000199936.4	P37059
HSD17B2	ENST00000566838.2	TSL:2	c.*218T>C	3_prime_UTR	Exon 3 of 3	ENSP00000456471.1	H3BRZ6
HSD17B2	ENST00000891334.1		c.802+355T>C	intron	N/A	ENSP00000561393.1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5534

AN:

152202

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.0318

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0579

Gnomad OTH

AF:

0.0497

GnomAD4 exome

AF:

0.0379

AC:

6140

AN:

161912

Hom.:

192

Cov.:

AF XY:

0.0355

AC XY:

3078

AN XY:

86790

show subpopulations

African (AFR)

AF:

0.00900

AC:

AN:

4776

American (AMR)

AF:

0.0323

AC:

205

AN:

6338

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

135

AN:

4334

East Asian (EAS)

AF:

0.00

AC:

AN:

6968

South Asian (SAS)

AF:

0.0101

AC:

272

AN:

27034

European-Finnish (FIN)

AF:

0.0377

AC:

285

AN:

7554

Middle Eastern (MID)

AF:

0.0229

AC:

AN:

612

European-Non Finnish (NFE)

AF:

0.0510

AC:

4883

AN:

95836

Other (OTH)

AF:

0.0358

AC:

303

AN:

8460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

277

553

830

1106

1383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.0363

AC:

5534

AN:

152320

Hom.:

153

Cov.:

AF XY:

0.0339

AC XY:

2527

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0100

AC:

416

AN:

41582

American (AMR)

AF:

0.0341

AC:

522

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00974

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0318

AC:

338

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0579

AC:

3939

AN:

68024

Other (OTH)

AF:

0.0492

AC:

104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

261

521

782

1042

1303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0430

Hom.:

Bravo

AF:

0.0359

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.34

(source)

DANN

Benign

0.48

PhyloP100

-1.2

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