Variant 1-228157753-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_020435.4(GJC2):c.-6G>C variant causes a 5 prime UTR change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 0 hom., cov: 0)

Exomes 𝑓: 0.18 ( 489 hom. )

Failed GnomAD Quality Control

Consequence

GJC2
NM_020435.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.69

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-228157753-G-C is Benign according to our data. Variant chr1-228157753-G-C is described in ClinVar as [Benign]. Clinvar id is 402902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC2	NM_020435.4 link	c.-6G>C		5_prime_UTR_variant	2/2	ENST00000366714.3	NP_065168.2	Q5T442A0A654IBV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC2	ENST00000366714 link	c.-6G>C		5_prime_UTR_variant	2/2	1	NM_020435.4	ENSP00000355675.2		Q5T442

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

9189

AN:

30906

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.446

AC:

36862

AN:

82652

Hom.:

AF XY:

0.446

AC XY:

19544

AN XY:

43866

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.180

AC:

98728

AN:

549468

Hom.:

489

Cov.:

AF XY:

0.192

AC XY:

53456

AN XY:

278490

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.297

AC:

9189

AN:

30890

Hom.:

Cov.:

AF XY:

0.271

AC XY:

4186

AN XY:

15474

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.406

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.00159

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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