chr16-82068323-C-G

Variant names:

• chr16-82068323-C-G
• rs766963607
• NM_002153.3:c.419C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002153.3(HSD17B2):​c.419C>G​(p.Thr140Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T140M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B2 NM_002153.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.419C>G	p.Thr140Arg	missense	Exon 2 of 5	NP_002144.1	P37059

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.419C>G	p.Thr140Arg	missense	Exon 2 of 5	ENSP00000199936.4	P37059
	HSD17B2	ENST00000891334.1		c.419C>G	p.Thr140Arg	missense	Exon 3 of 6	ENSP00000561393.1
	HSD17B2	ENST00000891335.1		c.419C>G	p.Thr140Arg	missense	Exon 3 of 6	ENSP00000561394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.72		Gain of MoRF binding (P = 0.0092)
MVP		0.94
MPC		0.025
ClinPred		0.99	D
GERP RS		5.2
PromoterAI		0.012	Neutral
Varity_R		0.85
gMVP		0.78

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: rs766963607; hg19: chr16-82101928;