7-102466033-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000292616.10(LRWD1):ā€‹c.297G>Cā€‹(p.Glu99Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

LRWD1
ENST00000292616.10 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.425
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3783435).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRWD1NM_152892.3 linkuse as main transcriptc.297G>C p.Glu99Asp missense_variant 2/15 ENST00000292616.10 NP_690852.1 Q9UFC0A0A140VJD0
LRWD1NM_001317721.2 linkuse as main transcriptc.-160G>C 5_prime_UTR_variant 2/15 NP_001304650.1 Q9UFC0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRWD1ENST00000292616.10 linkuse as main transcriptc.297G>C p.Glu99Asp missense_variant 2/151 NM_152892.3 ENSP00000292616.5 Q9UFC0

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461756
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 27, 2022The c.297G>C (p.E99D) alteration is located in exon 2 (coding exon 2) of the LRWD1 gene. This alteration results from a G to C substitution at nucleotide position 297, causing the glutamic acid (E) at amino acid position 99 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.99
D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.27
Sift
Benign
0.21
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.37
MutPred
0.54
Loss of disorder (P = 0.169);
MVP
0.61
MPC
0.33
ClinPred
0.83
D
GERP RS
-0.74
Varity_R
0.15
gMVP
0.49

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.

Other links and lift over

dbSNP: rs1797964057; hg19: chr7-102106480; API