Variant 2-20774929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.62

Variant links:

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]

LDAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2650708.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	4/7	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	4/7	1	NM_021925.4	ENSP00000237822	P1	Q9H6V9-1

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

543

AN:

152168

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00438

AC:

1101

AN:

251170

Hom.:

AF XY:

0.00439

AC XY:

596

AN XY:

135774

show subpopulations

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 SAS exome

AF:

0.00216

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.:

Cov.:

AF XY:

0.00445

AC XY:

3231

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00357

AC:

543

AN:

152286

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00417

AC:

506

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00368

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

LDAH: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.032

T;T;T;T;.;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D

MetaRNN

Benign

0.018

T;T;T;T;T;T;T

MetaSVM

Benign

-0.41

MutationTaster

Benign

1.0

D;D;D;D;D;D

PROVEAN

Benign

-1.8

N;.;N;N;.;N;N

REVEL

Benign

0.18

Sift

Benign

0.072

T;.;T;D;.;T;D

Sift4G

Benign

0.081

T;T;T;T;T;.;D

Polyphen

0.93

P;.;P;P;.;.;.

Vest4

0.51

MVP

0.46

MPC

0.28

ClinPred

0.016

GERP RS

5.0

Varity_R

0.62

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over