1-228157745-G-C

Position:

• chr1-228157745-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020435.4(GJC2):​c.-14G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (0 hom., cov: 0)
  • Exomes 𝑓: 0.16 (3789 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJC2 NM_020435.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.278

Genes affected

GJC2 (HGNC:17494): (gap junction protein gamma 2) This gene encodes a gap junction protein. Gap junction proteins are members of a large family of homologous connexins and comprise 4 transmembrane, 2 extracellular, and 3 cytoplasmic domains. This gene plays a key role in central myelination and is involved in peripheral myelination in humans. Defects in this gene are the cause of autosomal recessive Pelizaeus-Merzbacher-like disease-1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-228157745-G-C is Benign according to our data. Variant chr1-228157745-G-C is described in ClinVar as [Benign]. Clinvar id is 402901.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-228157745-G-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC2	NM_020435.4	c.-14G>C		5_prime_UTR_variant	2/2	ENST00000366714.3	NP_065168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC2	ENST00000366714	c.-14G>C		5_prime_UTR_variant	2/2	1	NM_020435.4	ENSP00000355675.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10434 AN: 48694 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.237

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.161 AC: 106630 AN: 662238 Hom.: 3789 Cov.: 21 AF XY: 0.172 AC XY: 58290 AN XY: 338530

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.214 AC: 10437 AN: 48658 Hom.: 0 Cov.: 0 AF XY: 0.201 AC XY: 4810 AN XY: 23878

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.237

Alfa AF: 0.00116 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs745809174; hg19: chr1-228345446;