16-82068344-A-C

Position:

• chr16-82068344-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002153.3(HSD17B2):​c.440A>C​(p.Asp147Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B2 NM_002153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20551684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.440A>C	p.Asp147Ala	missense_variant	2/5	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.440A>C	p.Asp147Ala	missense_variant	2/4		XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.440A>C	p.Asp147Ala	missense_variant	2/5	1	NM_002153.3	ENSP00000199936.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

HSD17B2: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.52
DEOGEN2	Benign	0.42	T;T;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.63	T;T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.41	.;N;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.21	T;T;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T
Polyphen		0.044	.;B;.;.;.
Vest4		0.15
MutPred		0.41		.;Gain of MoRF binding (P = 0.0607);.;.;.;
MVP		0.77
MPC		0.0059
ClinPred		0.82	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-82101949;