rs2042429

Variant names:

• chr16-82079866-C-T
• rs2042429
• NM_002153.3:c.664+8739C>T

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+8739C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,970 control chromosomes in the GnomAD database, including 24,423 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 0.56 (24423 hom., cov: 32)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.664+8739C>T		intron_variant	Intron 3 of 4	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.664+8739C>T		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+8739C>T		intron_variant	Intron 3 of 4	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.256+8739C>T		intron_variant	Intron 3 of 4	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.292+8739C>T		intron_variant	Intron 2 of 2	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.2	n.44-8677G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85501 AN: 151852 Hom.: 24379 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.563 AC: 85602 AN: 151970 Hom.: 24423 Cov.: 32 AF XY: 0.560 AC XY: 41603 AN XY: 74268

African (AFR) AF: 0.640 AC: 26546 AN: 41448

American (AMR) AF: 0.611 AC: 9327 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1554 AN: 3462

East Asian (EAS) AF: 0.314 AC: 1625 AN: 5172

South Asian (SAS) AF: 0.462 AC: 2224 AN: 4812

European-Finnish (FIN) AF: 0.527 AC: 5549 AN: 10536

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37016 AN: 67962

Other (OTH) AF: 0.535 AC: 1128 AN: 2108

Alfa AF: 0.548 Hom.: 46090

Bravo AF: 0.572

Asia WGS AF: 0.439 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.64
PhyloP100		0.18
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: rs2042429; hg19: chr16-82113471;