2-100286962-T-A

Position:

• chr2-100286962-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198461.4(LONRF2):​c.2022A>T​(p.Gln674His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LONRF2 NM_198461.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.330

Genes affected

LONRF2 (HGNC:24788): (LON peptidase N-terminal domain and ring finger 2) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2833897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF2	NM_198461.4	c.2022A>T	p.Gln674His	missense_variant	11/12	ENST00000393437.8	NP_940863.3
LONRF2	NM_001371783.1	c.1293A>T	p.Gln431His	missense_variant	12/13		NP_001358712.1
LONRF2	XM_047443537.1	c.1293A>T	p.Gln431His	missense_variant	11/12		XP_047299493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF2	ENST00000393437.8	c.2022A>T	p.Gln674His	missense_variant	11/12	5	NM_198461.4	ENSP00000377086.3
LONRF2	ENST00000409647.1	c.1293A>T	p.Gln431His	missense_variant	11/12	2		ENSP00000386823.1

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

Jul 19, 2023

The c.2022A>T (p.Q674H) alteration is located in exon 11 (coding exon 11) of the LONRF2 gene. This alteration results from a A to T substitution at nucleotide position 2022, causing the glutamine (Q) at amino acid position 674 to be replaced by a histidine (H). 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	Uncertain	0.56
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;T
Sift4G	Uncertain	0.016	D;T
Polyphen		0.97	D;.
Vest4		0.44
MutPred		0.50		Gain of catalytic residue at L676 (P = 0.0695);.;
MVP		0.44
MPC		0.90
ClinPred		0.99	D
GERP RS		-1.9
Varity_R		0.43
gMVP		0.71

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: chr2-100903424;