2-43935027-A-G

Position:

• chr2-43935027-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133259.4(LRPPRC):​c.2505-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 591,592 control chromosomes in the GnomAD database, including 8,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1538 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6927 hom.)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.226

Genes affected

LRPPRC (HGNC:15714): (leucine rich pentatricopeptide repeat containing) This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome. [provided by RefSeq, Mar 2012]

LRPPRC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-43935027-A-G is Benign according to our data. Variant chr2-43935027-A-G is described in ClinVar as [Benign]. Clinvar id is 676252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.2505-149T>C		intron_variant		ENST00000260665.12	NP_573566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.2505-149T>C		intron_variant		1	NM_133259.4	ENSP00000260665.7

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16246 AN: 152036 Hom.: 1526 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.138 AC: 60545 AN: 439434 Hom.: 6927 AF XY: 0.142 AC XY: 32806 AN XY: 231680

Gnomad4 AFR exome AF: 0.0357

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.0831

Gnomad4 NFE exome AF: 0.0987

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.107 AC: 16277 AN: 152158 Hom.: 1538 Cov.: 32 AF XY: 0.110 AC XY: 8164 AN XY: 74392

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0691

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.123

Alfa AF: 0.105 Hom.: 222

Bravo AF: 0.113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11899538; hg19: chr2-44162166;