rs2046325

Positions:

• chr2-20739946-T-C

Variant summary

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

The NM_021925.4(LDAH):​c.703+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,528,078 control chromosomes in the GnomAD database, including 75,023 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 0.25 (6026 hom., cov: 33)
  • Exomes 𝑓: 0.31 (68997 hom.)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

Genes affected

LDAH (HGNC:26145): (lipid droplet associated hydrolase) Predicted to enable lipase activity. Predicted to be involved in lipid storage. Predicted to be located in endoplasmic reticulum. Predicted to be active in lipid droplet. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4	c.703+25A>G		intron_variant		ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.703+25A>G		intron_variant		1	NM_021925.4	ENSP00000237822	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38215 AN: 151924 Hom.: 6019 Cov.: 33

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.327 AC: 80777 AN: 246952 Hom.: 14313 AF XY: 0.338 AC XY: 45215 AN XY: 133776

Gnomad AFR exome AF: 0.0548

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.380

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.307 AC: 422329 AN: 1376036 Hom.: 68997 Cov.: 21 AF XY: 0.313 AC XY: 215385 AN XY: 688902

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.251 AC: 38215 AN: 152042 Hom.: 6026 Cov.: 33 AF XY: 0.259 AC XY: 19242 AN XY: 74300

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.300

Alfa AF: 0.280 Hom.: 1909

Bravo AF: 0.240

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.84
DANN	Benign	0.85

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: rs2046325; hg19: chr2-20939706;