chr2-20747795-C-T

Variant names:

• chr2-20747795-C-T
• rs679397
• NM_021925.4:c.469-7590G>A

Variant summary

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

The NM_021925.4(LDAH):​c.469-7590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 152,302 control chromosomes in the GnomAD database, including 74,823 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 0.99 (74823 hom., cov: 31)
• Consequence: LDAH NM_021925.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021925.4. 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
	LDAH	NM_021925.4	MANE Select	c.469-7590G>A		intron	N/A	NP_068744.1	Q9H6V9-1
	LDAH	NM_001282719.2		c.343-7590G>A		intron	N/A	NP_001269648.1	A0A0A0MSH6
	LDAH	NM_001282720.2		c.325-7590G>A		intron	N/A	NP_001269649.1	Q9H6V9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDAH	ENST00000237822.8	TSL:1 MANE Select	c.469-7590G>A		intron	N/A	ENSP00000237822.3	Q9H6V9-1
	LDAH	ENST00000911673.1		c.469-7590G>A		intron	N/A	ENSP00000581732.1
	LDAH	ENST00000381090.7	TSL:5	c.469-7590G>A		intron	N/A	ENSP00000370480.3	B5MDU6

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150840 AN: 152184 Hom.: 74764 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.987

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.989

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

GnomAD4 genome AF: 0.991 AC: 150958 AN: 152302 Hom.: 74823 Cov.: 31 AF XY: 0.991 AC XY: 73797 AN XY: 74464

African (AFR) AF: 0.998 AC: 41501 AN: 41582

American (AMR) AF: 0.992 AC: 15172 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3290 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.998 AC: 4820 AN: 4832

European-Finnish (FIN) AF: 0.987 AC: 10490 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67227 AN: 68006

Other (OTH) AF: 0.990 AC: 2092 AN: 2114

Alfa AF: 0.989 Hom.: 4170

Bravo AF: 0.992

Asia WGS AF: 0.999 AC: 3464 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
DANN	Benign	0.45
PhyloP100		-2.5
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: rs679397; hg19: chr2-20947555;