rs759773695

Variant names:

• chr2-20790332-C-G
• NM_021925.4:c.221G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-20790332-C-G
• chr2-20790332-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021925.4(LDAH):​c.221G>C​(p.Arg74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LDAH NM_021925.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAH	NM_021925.4	c.221G>C	p.Arg74Pro	missense_variant	Exon 3 of 7	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8	c.221G>C	p.Arg74Pro	missense_variant	Exon 3 of 7	1	NM_021925.4	ENSP00000237822.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;T;T;.;.
Eigen	Benign	0.043
Eigen_PC	Benign	-0.00095
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.64	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.030	D;D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;D;D
Polyphen		0.99	D;B;B;.;.
Vest4		0.60
MutPred		0.54		Loss of catalytic residue at R74 (P = 0.0256);Loss of catalytic residue at R74 (P = 0.0256);Loss of catalytic residue at R74 (P = 0.0256);.;Loss of catalytic residue at R74 (P = 0.0256);
MVP		0.47
MPC		0.56
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.74
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-20990092;