chr2-20774929-C-T

Variant names:

• chr2-20774929-C-T
• rs145002349
• NM_021925.4:c.349G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021925.4(LDAH):​c.349G>A​(p.Glu117Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,613,080 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (26 hom.)
• Consequence: LDAH NM_021925.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62
• 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 (MetaRNN=0.017840356).
• BP6: Variant 2-20774929-C-T is Benign according to our data. Variant chr2-20774929-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.349G>A	p.Glu117Lys	missense	Exon 4 of 7	NP_068744.1	Q9H6V9-1
	LDAH	NM_001282719.2		c.223G>A	p.Glu75Lys	missense	Exon 3 of 6	NP_001269648.1	A0A0A0MSH6
	LDAH	NM_001282720.2		c.205G>A	p.Glu69Lys	missense	Exon 3 of 6	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.349G>A	p.Glu117Lys	missense	Exon 4 of 7	ENSP00000237822.3	Q9H6V9-1
	LDAH	ENST00000911673.1		c.349G>A	p.Glu117Lys	missense	Exon 4 of 8	ENSP00000581732.1
	LDAH	ENST00000381090.7	TSL:5	c.349G>A	p.Glu117Lys	missense	Exon 4 of 9	ENSP00000370480.3	B5MDU6

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 543 AN: 152168 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00438 AC: 1101 AN: 251170 AF XY: 0.00439

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.00492

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00458 AC: 6689 AN: 1460794 Hom.: 26 Cov.: 31 AF XY: 0.00445 AC XY: 3231 AN XY: 726598

African (AFR) AF: 0.000418 AC: 14 AN: 33454

American (AMR) AF: 0.00177 AC: 79 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 63 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00252 AC: 217 AN: 86192

European-Finnish (FIN) AF: 0.0177 AC: 947 AN: 53412

Middle Eastern (MID) AF: 0.000555 AC: 3 AN: 5406

European-Non Finnish (NFE) AF: 0.00462 AC: 5130 AN: 1111512

Other (OTH) AF: 0.00391 AC: 236 AN: 60346

GnomAD4 genome AF: 0.00357 AC: 543 AN: 152286 Hom.: 5 Cov.: 32 AF XY: 0.00384 AC XY: 286 AN XY: 74470

African (AFR) AF: 0.00113 AC: 47 AN: 41556

American (AMR) AF: 0.00346 AC: 53 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00388 AC: 264 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00365 Hom.: 3

Bravo AF: 0.00284

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00417 AC: 506

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00368

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.41	T
PhyloP100		2.6
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.072	T
Sift4G	Benign	0.081	T
Polyphen		0.93	P
Vest4		0.51
MVP		0.46
MPC		0.28
ClinPred		0.016	T
GERP RS		5.0
Varity_R		0.62
gMVP		0.57
Mutation Taster		=249/51	polymorphism

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: rs145002349; hg19: chr2-20974689; COSMIC: COSV99426124;