rs2576060

Variant names:

• chr18-47110735-T-C
• rs2576060
• NM_032124.5:c.677-1950A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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.

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.677-1950A>G		intron	N/A	NP_115500.1
	HDHD2	NM_001318765.2		c.407-1950A>G		intron	N/A	NP_001305694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD2	ENST00000300605.11	TSL:1 MANE Select	c.677-1950A>G		intron	N/A	ENSP00000300605.4
	HDHD2	ENST00000588183.5	TSL:1	n.*549-1950A>G		intron	N/A	ENSP00000466602.1
	HDHD2	ENST00000851063.1		c.676+2242A>G		intron	N/A	ENSP00000521128.1

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

African (AFR) AF: 0.425 AC: 6699 AN: 15772

American (AMR) AF: 0.445 AC: 437 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 2543 AN: 5140

East Asian (EAS) AF: 0.210 AC: 761 AN: 3630

South Asian (SAS) AF: 0.370 AC: 6093 AN: 16448

European-Finnish (FIN) AF: 0.467 AC: 129 AN: 276

Middle Eastern (MID) AF: 0.477 AC: 773 AN: 1620

European-Non Finnish (NFE) AF: 0.454 AC: 345452 AN: 761372

Other (OTH) AF: 0.434 AC: 11839 AN: 27284

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

African (AFR) AF: 0.417 AC: 17313 AN: 41478

American (AMR) AF: 0.443 AC: 6774 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5168

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5024 AN: 10554

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30786 AN: 67964

Other (OTH) AF: 0.443 AC: 934 AN: 2108

Alfa AF: 0.449 Hom.: 9889

Bravo AF: 0.435

Asia WGS AF: 0.292 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs2576060; hg19: chr18-44637106;