8-104490836-A-C

Variant names:

• chr8-104490836-A-C
• NM_013437.5:c.2417T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013437.5(LRP12):​c.2417T>G​(p.Leu806Arg) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP12 NM_013437.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

LRP12 (HGNC:31708): (LDL receptor related protein 12) This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

LRP12 Gene-Disease associations (from GenCC):

• oculopharyngodistal myopathy 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06378487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP12	NM_013437.5	c.2417T>G	p.Leu806Arg	missense_variant	Exon 7 of 7	ENST00000276654.10	NP_038465.1
LRP12	NM_001135703.3	c.2360T>G	p.Leu787Arg	missense_variant	Exon 6 of 6		NP_001129175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP12	ENST00000276654.10	c.2417T>G	p.Leu806Arg	missense_variant	Exon 7 of 7	1	NM_013437.5	ENSP00000276654.5
LRP12	ENST00000424843.6	c.2360T>G	p.Leu787Arg	missense_variant	Exon 6 of 6	2		ENSP00000399148.2
LRP12	ENST00000518375.1	n.1770T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2417T>G (p.L806R) alteration is located in exon 7 (coding exon 7) of the LRP12 gene. This alteration results from a T to G substitution at nucleotide position 2417, causing the leucine (L) at amino acid position 806 to be replaced by an arginine (R). 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	0.073
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.092	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	.;N
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.12
Sift	Benign	0.36	T;T
Sift4G	Benign	0.098	T;T
Polyphen		0.062	B;B
Vest4		0.23
MutPred		0.13		.;Gain of methylation at L806 (P = 0.0631);
MVP		0.26
MPC		0.36
ClinPred		0.15	T
GERP RS		3.1
Varity_R		0.15
gMVP		0.14
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr8-105503064;