Genetic Variant NM_020435.4:c.-14G>C (chr1-228157745-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.278

Variant links:

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]

GJC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
GJC2	NM_020435.4 link	c.-14G>C		5_prime_UTR_variant	Exon 2 of 2	ENST00000366714.3	NP_065168.2	Q5T442A0A654IBV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJC2	ENST00000366714 link	c.-14G>C		5_prime_UTR_variant	Exon 2 of 2	1	NM_020435.4	ENSP00000355675.2		Q5T442

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

10434

AN:

48694

Hom.:

Cov.:

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.:

AF XY:

0.172

AC XY:

58290

AN XY:

338530

show subpopulations

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.:

Cov.:

AF XY:

0.201

AC XY:

4810

AN XY:

23878

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over