16-82068294-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002153.3(HSD17B2):c.390G>A(p.Pro130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,066 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (9 hom.)
• Consequence: HSD17B2 NM_002153.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.213

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-82068294-G-A is Benign according to our data. Variant chr16-82068294-G-A is described in ClinVar as [Benign]. Clinvar id is 713204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.390G>A	p.Pro130=	synonymous_variant	2/5	ENST00000199936.9
HSD17B2	XM_047434049.1	c.390G>A	p.Pro130=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.390G>A	p.Pro130=	synonymous_variant	2/5	1	NM_002153.3	P1
HSD17B2-AS1	ENST00000567021.1	n.430+2509C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00141 AC: 354 AN: 251378 Hom.: 1 AF XY: 0.00160 AC XY: 217 AN XY: 135862

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.000740

Gnomad NFE exome AF: 0.00204

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00165 AC: 2413 AN: 1461836 Hom.: 9 Cov.: 31 AF XY: 0.00176 AC XY: 1282 AN XY: 727214

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00314

Gnomad4 FIN exome AF: 0.000973

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74446

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.000990

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.0
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs34731990; hg19: chr16-82101899;