rs2955162

Positions:

• chr16-82095172-C-T

Variant summary

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

The NM_002153.3(HSD17B2):​c.803-2903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,024 control chromosomes in the GnomAD database, including 4,833 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 0.25 (4828 hom., cov: 32)
  • Exomes 𝑓: 0.31 (5 hom.)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.803-2903C>T		intron_variant		ENST00000199936.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.803-2903C>T		intron_variant		1	NM_002153.3	P1
HSD17B2-AS1	ENST00000567021.1	n.44-23983G>A		intron_variant, non_coding_transcript_variant		5
HSD17B2	ENST00000566838.2	c.*3996C>T		3_prime_UTR_variant	3/3	2
HSD17B2	ENST00000568090.5	c.395-2903C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37606 AN: 151844 Hom.: 4818 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.306 AC: 19 AN: 62 Hom.: 5 Cov.: 0 AF XY: 0.321 AC XY: 9 AN XY: 28

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.248 AC: 37642 AN: 151962 Hom.: 4828 Cov.: 32 AF XY: 0.247 AC XY: 18350 AN XY: 74264

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.246

Alfa AF: 0.262 Hom.: 7780

Bravo AF: 0.240

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs2955162; hg19: chr16-82128777;