16-82090956-C-G

Position:

• chr16-82090956-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002153.3(HSD17B2):​c.719C>G​(p.Thr240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,614,002 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (13 hom.)
• Consequence: HSD17B2 NM_002153.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.913

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005624205).
• BP6: Variant 16-82090956-C-G is Benign according to our data. Variant chr16-82090956-C-G is described in ClinVar as [Benign]. Clinvar id is 781228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00945 (1440/152302) while in subpopulation AFR AF= 0.033 (1371/41558). AF 95% confidence interval is 0.0315. There are 24 homozygotes in gnomad4. There are 682 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.719C>G	p.Thr240Ser	missense_variant	4/5	ENST00000199936.9	NP_002144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.719C>G	p.Thr240Ser	missense_variant	4/5	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.311C>G	p.Thr104Ser	missense_variant	4/5	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.347C>G	p.Thr116Ser	missense_variant	3/3	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.1	n.44-19767G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00944 AC: 1437 AN: 152184 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00254 AC: 637 AN: 251188 Hom.: 8 AF XY: 0.00177 AC XY: 240 AN XY: 135766

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000890 AC: 1301 AN: 1461700 Hom.: 13 Cov.: 31 AF XY: 0.000738 AC XY: 537 AN XY: 727160

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome AF: 0.00945 AC: 1440 AN: 152302 Hom.: 24 Cov.: 32 AF XY: 0.00916 AC XY: 682 AN XY: 74452

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.000726 Hom.: 3

Bravo AF: 0.0109

ESP6500AA AF: 0.0316 AC: 139

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00307 AC: 373

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.2
DANN	Benign	0.54
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.58	T;T;T
MetaRNN	Benign	0.0056	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.44	N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.47	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.55	T;T;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.22
MutPred		0.51		Gain of disorder (P = 0.0207);.;.;
MVP		0.46
MPC		0.0065
ClinPred		0.0028	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75102012; hg19: chr16-82124561;