chr1-204618999-G-T

Position:

• chr1-204618999-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000367177.4(LRRN2):​c.994C>A​(p.His332Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRN2 ENST00000367177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08

Genes affected

LRRN2 (HGNC:16914): (leucine rich repeat neuronal 2) The protein encoded by this gene belongs to the leucine-rich repeat superfamily. This gene was found to be amplified and overexpressed in malignant gliomas. The encoded protein has homology with other proteins that function as cell-adhesion molecules or as signal transduction receptors and is a candidate for the target gene in the 1q32.1 amplicon in malignant gliomas. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

LOC105371692 (HGNC:):

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=0.16482154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRN2	NM_201630.2	c.994C>A	p.His332Asn	missense_variant	2/2	ENST00000367177.4	NP_963924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRN2	ENST00000367177.4	c.994C>A	p.His332Asn	missense_variant	2/2	1	NM_201630.2	ENSP00000356145.3
LRRN2	ENST00000367176.7	c.994C>A	p.His332Asn	missense_variant	3/3	1		ENSP00000356144.3
LRRN2	ENST00000367175.1	c.994C>A	p.His332Asn	missense_variant	1/1	6		ENSP00000356143.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

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

Aug 30, 2022

The c.994C>A (p.H332N) alteration is located in exon 3 (coding exon 1) of the LRRN2 gene. This alteration results from a C to A substitution at nucleotide position 994, causing the histidine (H) at amino acid position 332 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.0080	T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	.;.;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.26	N;N;N
MutationTaster	Benign	0.59	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.074	B;B;B
Vest4		0.27
MutPred		0.18		Loss of catalytic residue at L334 (P = 0.0611);Loss of catalytic residue at L334 (P = 0.0611);Loss of catalytic residue at L334 (P = 0.0611);
MVP		0.65
MPC		0.66
ClinPred		0.34	T
GERP RS		5.7
Varity_R		0.14
gMVP		0.49

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: chr1-204588127;