2-20728282-T-C

Variant names:

• chr2-20728282-T-C
• rs10495709
• NM_021925.4:c.703+11689A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021925.4(LDAH):​c.703+11689A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,926 control chromosomes in the GnomAD database, including 4,469 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 0.22 (4469 hom., cov: 32)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.703+11689A>G		intron_variant	Intron 5 of 6	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.703+11689A>G		intron_variant	Intron 5 of 6	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33671 AN: 151808 Hom.: 4462 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33691 AN: 151926 Hom.: 4469 Cov.: 32 AF XY: 0.227 AC XY: 16817 AN XY: 74228

African (AFR) AF: 0.0818 AC: 3398 AN: 41518

American (AMR) AF: 0.281 AC: 4296 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 453 AN: 3466

East Asian (EAS) AF: 0.356 AC: 1831 AN: 5146

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4816

European-Finnish (FIN) AF: 0.352 AC: 3702 AN: 10528

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17914 AN: 67882

Other (OTH) AF: 0.194 AC: 410 AN: 2108

Alfa AF: 0.228 Hom.: 2669

Bravo AF: 0.215

Asia WGS AF: 0.285 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		1.7
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: rs10495709; hg19: chr2-20928042;