rs2966245

Variant names:

• chr16-82072694-G-A
• rs2966245
• NM_002153.3:c.664+1567G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002153.3(HSD17B2):​c.664+1567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,022 control chromosomes in the GnomAD database, including 26,968 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 0.59 (26968 hom., cov: 32)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.664+1567G>A		intron_variant	Intron 3 of 4	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.664+1567G>A		intron_variant	Intron 3 of 3		XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.664+1567G>A		intron_variant	Intron 3 of 4	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.256+1567G>A		intron_variant	Intron 3 of 4	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.292+1567G>A		intron_variant	Intron 2 of 2	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.2	n.44-1505C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89873 AN: 151904 Hom.: 26928 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 89974 AN: 152022 Hom.: 26968 Cov.: 32 AF XY: 0.589 AC XY: 43773 AN XY: 74296

African (AFR) AF: 0.646 AC: 26764 AN: 41436

American (AMR) AF: 0.646 AC: 9868 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1601 AN: 3464

East Asian (EAS) AF: 0.328 AC: 1696 AN: 5178

South Asian (SAS) AF: 0.468 AC: 2254 AN: 4820

European-Finnish (FIN) AF: 0.580 AC: 6121 AN: 10550

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39809 AN: 67976

Other (OTH) AF: 0.574 AC: 1211 AN: 2110

Alfa AF: 0.584 Hom.: 76334

Bravo AF: 0.599

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.72
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2966245; hg19: chr16-82106299;