16-82035539-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002153.3(HSD17B2):c.115G>A(p.Val39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HSD17B2 NM_002153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.136

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11409572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.115G>A	p.Val39Ile	missense_variant	1/5	ENST00000199936.9
HSD17B2	XM_047434049.1	c.115G>A	p.Val39Ile	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.115G>A	p.Val39Ile	missense_variant	1/5	1	NM_002153.3	P1
HSD17B2	ENST00000566213.1	c.115G>A	p.Val39Ile	missense_variant	1/2	3
HSD17B2	ENST00000563491.5	c.-144+391G>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.115G>A (p.V39I) alteration is located in exon 1 (coding exon 1) of the HSD17B2 gene. This alteration results from a G to A substitution at nucleotide position 115, causing the valine (V) at amino acid position 39 to be replaced by an isoleucine (I). 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	Benign	0.084
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	1.0
Dann	Benign	0.97
DEOGEN2	Benign	0.047	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.20
Sift	Benign	0.22	T;T
Sift4G	Uncertain	0.055	T;D
Polyphen		0.13	B;.
Vest4		0.060
MutPred		0.21		Loss of catalytic residue at V39 (P = 0.0542);Loss of catalytic residue at V39 (P = 0.0542);
MVP		0.44
MPC		0.0060
ClinPred		0.12	T
GERP RS		0.023
Varity_R		0.028
gMVP		0.086

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-82069144;