GeneBe

16-82098435-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_002153.3(HSD17B2):​c.1163A>T​(p.Ter388Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

HSD17B2
NM_002153.3 stop_lost

Scores

7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_002153.3 Downstream stopcodon found after 444 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B2NM_002153.3 linkc.1163A>T p.Ter388Leuext*? stop_lost Exon 5 of 5 ENST00000199936.9 NP_002144.1 P37059

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B2ENST00000199936.9 linkc.1163A>T p.Ter388Leuext*? stop_lost Exon 5 of 5 1 NM_002153.3 ENSP00000199936.4 P37059
HSD17B2ENST00000566838.2 linkc.*7259A>T 3_prime_UTR_variant Exon 3 of 3 2 ENSP00000456471.1 H3BRZ6
HSD17B2-AS1ENST00000567021.2 linkn.44-27246T>A intron_variant Intron 1 of 3 5
HSD17B2ENST00000568090.5 linkc.*94A>T downstream_gene_variant 3 ENSP00000456529.1 H3BS44

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1437190
Hom.:
0
Cov.:
32
AF XY:
0.00000140
AC XY:
1
AN XY:
712564
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
32292
American (AMR)
AF:
0.00
AC:
0
AN:
40596
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24820
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39428
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82322
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52504
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5620
European-Non Finnish (NFE)
AF:
9.09e-7
AC:
1
AN:
1100400
Other (OTH)
AF:
0.00
AC:
0
AN:
59208
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
4.3
DANN
Benign
0.82
Eigen
Benign
0.13
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.058
N
PhyloP100
0.26
Vest4
0.061
GERP RS
0.67

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

Other links and lift over

dbSNP: rs8191246; hg19: chr16-82132040; API