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GeneBe

16-82070998-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002153.3(HSD17B2):​c.535C>T​(p.Leu179Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HSD17B2
NM_002153.3 missense

Scores

11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.794
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSD17B2NM_002153.3 linkuse as main transcriptc.535C>T p.Leu179Phe missense_variant 3/5 ENST00000199936.9
HSD17B2XM_047434049.1 linkuse as main transcriptc.535C>T p.Leu179Phe missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSD17B2ENST00000199936.9 linkuse as main transcriptc.535C>T p.Leu179Phe missense_variant 3/51 NM_002153.3 P1
HSD17B2-AS1ENST00000567021.1 linkuse as main transcriptn.235G>A non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251458
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461866
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 27, 2022The c.535C>T (p.L179F) alteration is located in exon 3 (coding exon 3) of the HSD17B2 gene. This alteration results from a C to T substitution at nucleotide position 535, causing the leucine (L) at amino acid position 179 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;D;T;.;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.83
T;T;T;T;T;T
M_CAP
Benign
0.068
D
MetaRNN
Uncertain
0.67
D;D;D;D;D;D
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D;D
Sift
Uncertain
0.0070
D;D;D;T;D;T
Sift4G
Benign
0.34
T;T;D;T;D;T
Polyphen
1.0
.;D;.;.;.;.
Vest4
0.58
MVP
0.98
MPC
0.025
ClinPred
0.97
D
GERP RS
4.9
Varity_R
0.66
gMVP
0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372223061; hg19: chr16-82104603; API