Genetic Variant NM_174911.5:c.805C>T (chr8-126556585-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_174911.5(LRATD2):c.805C>T(p.Leu269Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L269V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LRATD2
NM_174911.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.83

Publications

0 publications found

Variant links:

Genes affected

LRATD2 (HGNC:24166): (LRAT domain containing 2) Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRATD2 links:

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

PCAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRATD2	NM_174911.5 link	c.805C>T	p.Leu269Phe	missense_variant	Exon 2 of 2	ENST00000304916.4	NP_777571.1	Q96KN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRATD2	ENST00000304916.4 link	c.805C>T	p.Leu269Phe	missense_variant	Exon 2 of 2	1	NM_174911.5	ENSP00000302578.3	Q96KN1
LRATD2	ENST00000652209.1 link	c.805C>T	p.Leu269Phe	missense_variant	Exon 1 of 1			ENSP00000498944.1	Q96KN1
PCAT1	ENST00000524320.2 link	n.263G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
LRATD2	ENST00000517458.1 link	n.-166C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000416

AC:

AN:

240406

AF XY:

0.00000757

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457414

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724592

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110096

Other (OTH)

AF:

0.00

AC:

AN:

60160

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

7.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

REVEL

Benign

0.21

Sift

Uncertain

0.028

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.69

MutPred

0.47

Loss of glycosylation at T271 (P = 0.1212);

MVP

0.57

MPC

1.8

ClinPred

0.92

GERP RS

4.0

Varity_R

0.20

gMVP

0.66

Mutation Taster

=51/49

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.

NM_174911.5:c.805C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over