Genetic Variant LRWD1:p.Ala202Val (chr7-102467750-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152892.3(LRWD1):c.605C>T(p.Ala202Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,399,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

LRWD1
NM_152892.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

Publications

0 publications found

Variant links:

Genes affected

LRWD1 (HGNC:21769): (leucine rich repeats and WD repeat domain containing 1) The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

LRWD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12168315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152892.3. 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
	LRWD1	NM_152892.3	MANE Select	c.605C>T	p.Ala202Val	missense	Exon 5 of 15	NP_690852.1	Q9UFC0
	LRWD1	NM_001317721.2		c.149C>T	p.Ala50Val	missense	Exon 5 of 15	NP_001304650.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRWD1	ENST00000292616.10	TSL:1 MANE Select	c.605C>T	p.Ala202Val	missense	Exon 5 of 15	ENSP00000292616.5	Q9UFC0
LRWD1	ENST00000896262.1		c.605C>T	p.Ala202Val	missense	Exon 5 of 16	ENSP00000566321.1
LRWD1	ENST00000922655.1		c.605C>T	p.Ala202Val	missense	Exon 5 of 15	ENSP00000592714.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000191

AC:

AN:

156768

AF XY:

0.0000242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000495

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1399542

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31652

American (AMR)

AF:

0.00

AC:

AN:

35724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35832

South Asian (SAS)

AF:

0.00

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.00000556

AC:

AN:

1079198

Other (OTH)

AF:

0.00

AC:

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

M_CAP

Benign

0.048

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

3.6

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.091

Sift

Benign

0.084

Sift4G

Benign

0.17

Polyphen

0.0050

Vest4

0.20

MutPred

0.18

Loss of disorder (P = 0.1209)

MVP

0.71

MPC

0.059

ClinPred

0.14

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.57

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over