chr13-27548406-C-T

Position:

• chr13-27548406-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153371.4(LNX2):​c.2002G>A​(p.Val668Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNX2 NM_153371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

LNX2 (HGNC:20421): (ligand of numb-protein X 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX2	NM_153371.4	c.2002G>A	p.Val668Ile	missense_variant	10/10	ENST00000316334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX2	ENST00000316334.5	c.2002G>A	p.Val668Ile	missense_variant	10/10	1	NM_153371.4	P1
LNX2	ENST00000649248.1	c.2002G>A	p.Val668Ile	missense_variant	11/11			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000227

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

Feb 13, 2024

The c.2002G>A (p.V668I) alteration is located in exon 10 (coding exon 9) of the LNX2 gene. This alteration results from a G to A substitution at nucleotide position 2002, causing the valine (V) at amino acid position 668 to be replaced by an isoleucine (I). 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	0.31
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.65	N;.
REVEL	Benign	0.25
Sift	Benign	0.35	T;.
Sift4G	Benign	0.36	T;.
Polyphen		0.48	P;P
Vest4		0.24
MutPred		0.60		Gain of catalytic residue at S663 (P = 0);Gain of catalytic residue at S663 (P = 0);
MVP		0.59
MPC		1.2
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.074
gMVP		0.48

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

Other links and lift over

dbSNP: rs1421578167; hg19: chr13-28122543; COSMIC: COSV60334591;