16-82093225-C-G

Position:

• chr16-82093225-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002153.3(HSD17B2):​c.802+2186C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,062 control chromosomes in the GnomAD database, including 25,042 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 0.57 (25040 hom., cov: 32)
  • Exomes 𝑓: 0.60 (2 hom.)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.802+2186C>G		intron_variant		ENST00000199936.9	NP_002144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.802+2186C>G		intron_variant		1	NM_002153.3	ENSP00000199936	P1
HSD17B2-AS1	ENST00000567021.1	n.44-22036G>C		intron_variant, non_coding_transcript_variant		5
HSD17B2	ENST00000566838.2	c.*2049C>G		3_prime_UTR_variant	3/3	2		ENSP00000456471
HSD17B2	ENST00000568090.5	c.394+2186C>G		intron_variant		3		ENSP00000456529

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86801 AN: 151934 Hom.: 25029 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.600 AC: 6 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.571 AC: 86834 AN: 152052 Hom.: 25040 Cov.: 32 AF XY: 0.566 AC XY: 42053 AN XY: 74314

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.589

Alfa AF: 0.460 Hom.: 1241

Bravo AF: 0.567

Asia WGS AF: 0.471 AC: 1637 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs9934209; hg19: chr16-82126830;