rs2576060

chr18-47110735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032124.5(HDHD2):c.677-1950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 984,566 control chromosomes in the GnomAD database, including 99,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (14572 hom., cov: 32)
  • Exomes 𝑓: 0.45 (84575 hom.)
• Consequence: HDHD2 NM_032124.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDHD2	NM_032124.5	c.677-1950A>G		intron_variant		ENST00000300605.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDHD2	ENST00000300605.11	c.677-1950A>G		intron_variant		1	NM_032124.5	P1
HDHD2	ENST00000588183.5	c.*549-1950A>G		intron_variant, NMD_transcript_variant		1
HDHD2	ENST00000588861.1	n.122A>G		non_coding_transcript_exon_variant	1/1
HDHD2	ENST00000587841.5	n.381-1950A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66249 AN: 151924 Hom.: 14569 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.450 AC: 374726 AN: 832524 Hom.: 84575 Cov.: 30 AF XY: 0.451 AC XY: 173304 AN XY: 384484

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.436 AC: 66275 AN: 152042 Hom.: 14572 Cov.: 32 AF XY: 0.434 AC XY: 32223 AN XY: 74292

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.443

Alfa AF: 0.448 Hom.: 9000

Bravo AF: 0.435

Asia WGS AF: 0.292 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	11
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs2576060; hg19: chr18-44637106;