chr8-126556786-C-G

Position:

• chr8-126556786-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_174911.5(LRATD2):​c.604G>C​(p.Glu202Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRATD2 NM_174911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

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

LOC105375751 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRATD2	NM_174911.5	c.604G>C	p.Glu202Gln	missense_variant	2/2	ENST00000304916.4
LOC105375751	XR_007061097.1	n.243C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRATD2	ENST00000304916.4	c.604G>C	p.Glu202Gln	missense_variant	2/2	1	NM_174911.5	P1
LRATD2	ENST00000652209.1	c.604G>C	p.Glu202Gln	missense_variant	1/1			P1
PCAT1	ENST00000524320.2	n.464C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.604G>C (p.E202Q) alteration is located in exon 2 (coding exon 1) of the FAM84B gene. This alteration results from a G to C substitution at nucleotide position 604, causing the glutamic acid (E) at amino acid position 202 to be replaced by a glutamine (Q). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.96	D
Vest4		0.96
MutPred		0.50		Gain of catalytic residue at E202 (P = 0.0094);
MVP		0.56
MPC		1.8
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.50
gMVP		0.98

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: chr8-127569031;