1-204618348-G-A

Position:

• chr1-204618348-G-A

Variant summary

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

The NM_201630.2(LRRN2):​c.1645C>T​(p.Pro549Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: LRRN2 NM_201630.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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=0.12023941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRN2	NM_201630.2	c.1645C>T	p.Pro549Ser	missense_variant	2/2	ENST00000367177.4	NP_963924.1
LOC105371692	XR_007066814.1	n.22672G>A		non_coding_transcript_exon_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRN2	ENST00000367177.4	c.1645C>T	p.Pro549Ser	missense_variant	2/2	1	NM_201630.2	ENSP00000356145	P1
LRRN2	ENST00000367176.7	c.1645C>T	p.Pro549Ser	missense_variant	3/3	1		ENSP00000356144	P1
LRRN2	ENST00000367175.1	c.1645C>T	p.Pro549Ser	missense_variant	1/1			ENSP00000356143	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

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

Sep 06, 2022

The c.1645C>T (p.P549S) alteration is located in exon 3 (coding exon 1) of the LRRN2 gene. This alteration results from a C to T substitution at nucleotide position 1645, causing the proline (P) at amino acid position 549 to be replaced by a serine (S). 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	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.68
DEOGEN2	Benign	0.0051	T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	.;.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L
MutationTaster	Benign	0.76	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.26	N;N;N
REVEL	Benign	0.059
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.020	B;B;B
Vest4		0.047
MutPred		0.46		Gain of disorder (P = 0.1012);Gain of disorder (P = 0.1012);Gain of disorder (P = 0.1012);
MVP		0.15
MPC		0.48
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.052
gMVP		0.34

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: chr1-204587476;