chr7-102465132-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152892.3(LRWD1):​c.52G>T​(p.Asp18Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.3e-7 ( 0 hom. )

Consequence

LRWD1
NM_152892.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.375
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20047602).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRWD1NM_152892.3 linkc.52G>T p.Asp18Tyr missense_variant Exon 1 of 15 ENST00000292616.10 NP_690852.1 Q9UFC0A0A140VJD0
LRWD1NM_001317721.2 linkc.-423G>T 5_prime_UTR_variant Exon 1 of 15 NP_001304650.1 Q9UFC0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRWD1ENST00000292616.10 linkc.52G>T p.Asp18Tyr missense_variant Exon 1 of 15 1 NM_152892.3 ENSP00000292616.5 Q9UFC0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.32e-7
AC:
1
AN:
1366842
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
675824
show subpopulations
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:
0.0000133
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52G>T (p.D18Y) alteration is located in exon 1 (coding exon 1) of the LRWD1 gene. This alteration results from a G to T substitution at nucleotide position 52, causing the aspartic acid (D) at amino acid position 18 to be replaced by a tyrosine (Y). 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
0.19
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.0085
T;.
Eigen
Benign
-0.024
Eigen_PC
Benign
-0.014
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.86
D;T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.15
Sift
Uncertain
0.020
D;.
Sift4G
Uncertain
0.039
D;D
Polyphen
0.93
P;.
Vest4
0.26
MutPred
0.30
Gain of MoRF binding (P = 0.056);Gain of MoRF binding (P = 0.056);
MVP
0.74
MPC
3.1
ClinPred
0.63
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.092
gMVP
0.46

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: chr7-102105579; API