chr7-102465132-G-T

Variant names:

• chr7-102465132-G-T
• NM_152892.3:c.52G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.375

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]

ACMG classification

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
LRWD1	NM_152892.3	c.52G>T	p.Asp18Tyr	missense_variant	Exon 1 of 15	ENST00000292616.10	NP_690852.1
LRWD1	NM_001317721.2	c.-423G>T		5_prime_UTR_variant	Exon 1 of 15		NP_001304650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRWD1	ENST00000292616.10	c.52G>T	p.Asp18Tyr	missense_variant	Exon 1 of 15	1	NM_152892.3	ENSP00000292616.5

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

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

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;