2-20732518-T-C

Variant names:

• chr2-20732518-T-C
• rs340623
• NM_021925.4:c.703+7453A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021925.4(LDAH):​c.703+7453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,096 control chromosomes in the GnomAD database, including 11,040 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 0.36 (11040 hom., cov: 32)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.703+7453A>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+7453A>G		intron_variant	Intron 5 of 6	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54044 AN: 151978 Hom.: 11033 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.355 AC: 54049 AN: 152096 Hom.: 11040 Cov.: 32 AF XY: 0.362 AC XY: 26891 AN XY: 74370

African (AFR) AF: 0.147 AC: 6121 AN: 41530

American (AMR) AF: 0.457 AC: 6995 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2667 AN: 5172

South Asian (SAS) AF: 0.601 AC: 2891 AN: 4812

European-Finnish (FIN) AF: 0.366 AC: 3858 AN: 10544

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28212 AN: 67960

Other (OTH) AF: 0.425 AC: 898 AN: 2112

Alfa AF: 0.355 Hom.: 1379

Bravo AF: 0.348

Asia WGS AF: 0.547 AC: 1899 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		0.55
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: rs340623; hg19: chr2-20932278;