rs925115409

Variant names:

• chr18-47134502-A-G
• NM_032124.5:c.304T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-47134502-A-G
• chr18-47134502-A-T

Variant summary

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

The NM_032124.5(HDHD2):​c.304T>C​(p.Phe102Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. F102I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HDHD2 NM_032124.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDHD2	NM_032124.5	c.304T>C	p.Phe102Leu	missense_variant	Exon 3 of 7	ENST00000300605.11	NP_115500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDHD2	ENST00000300605.11	c.304T>C	p.Phe102Leu	missense_variant	Exon 3 of 7	1	NM_032124.5	ENSP00000300605.4
ENSG00000267228	ENST00000588705.1	n.*462T>C		downstream_gene_variant		2		ENSP00000465194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459932 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726346

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T;.;.;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.7	D;.;.;.;.;.;.
REVEL	Benign	0.22
Sift	Uncertain	0.019	D;.;.;.;.;.;.
Sift4G	Uncertain	0.060	T;.;D;.;D;.;D
Polyphen		0.19	B;.;.;.;.;.;.
Vest4		0.76
MutPred		0.70		Loss of methylation at K103 (P = 0.0531);Loss of methylation at K103 (P = 0.0531);.;Loss of methylation at K103 (P = 0.0531);Loss of methylation at K103 (P = 0.0531);Loss of methylation at K103 (P = 0.0531);.;
MVP		0.31
MPC		0.87
ClinPred		0.98	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.86

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: chr18-44660873;