rs2063700285

Variant names:

• chr18-47130253-T-G
• rs2063700285
• NM_032124.5:c.386A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032124.5(HDHD2):​c.386A>C​(p.Gln129Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HDHD2 NM_032124.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 0 publications found

Genes affected

HDHD2 (HGNC:25364): (haloacid dehalogenase like hydrolase domain containing 2) Enables enzyme binding activity. Predicted to be involved in dephosphorylation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267228 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29580104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032124.5. 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
	HDHD2	NM_032124.5	MANE Select	c.386A>C	p.Gln129Pro	missense	Exon 4 of 7	NP_115500.1	Q9H0R4-1
	HDHD2	NM_001318765.2		c.116A>C	p.Gln39Pro	missense	Exon 4 of 7	NP_001305694.1	Q9H0R4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD2	ENST00000300605.11	TSL:1 MANE Select	c.386A>C	p.Gln129Pro	missense	Exon 4 of 7	ENSP00000300605.4	Q9H0R4-1
	HDHD2	ENST00000588183.5	TSL:1	n.*258A>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000466602.1	K7EKX8
	HDHD2	ENST00000588183.5	TSL:1	n.*258A>C		3_prime_UTR	Exon 4 of 7	ENSP00000466602.1	K7EKX8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.4
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.15
Sift	Benign	0.054	T
Sift4G	Uncertain	0.032	D
Polyphen		0.0090	B
Vest4		0.69
MutPred		0.56		Gain of catalytic residue at Q129 (P = 0.1058)
MVP		0.30
MPC		0.31
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.82
gMVP		0.90

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: rs2063700285; hg19: chr18-44656624;