Variant 1-228158724-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020435.4(GJC2):c.966G>C(p.Ala322Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,318,888 control chromosomes in the GnomAD database, including 1,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 220 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1146 hom. )

Consequence

GJC2
NM_020435.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.222

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-228158724-G-C is Benign according to our data. Variant chr1-228158724-G-C is described in ClinVar as [Benign]. Clinvar id is 261257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-228158724-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.222 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC2	NM_020435.4 linkuse as main transcript	c.966G>C	p.Ala322Ala	synonymous_variant	2/2	ENST00000366714.3	NP_065168.2	Q5T442A0A654IBV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC2	ENST00000366714.3 linkuse as main transcript	c.966G>C	p.Ala322Ala	synonymous_variant	2/2	1	NM_020435.4	ENSP00000355675.2		Q5T442

Frequencies

GnomAD3 genomes

AF:

0.0505

AC:

7430

AN:

147044

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0558

Gnomad AMI

AF:

0.0277

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0421

Gnomad FIN

AF:

0.0630

Gnomad MID

AF:

0.0419

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0444

GnomAD3 exomes

AF:

0.0411

AC:

1910

AN:

46506

Hom.:

AF XY:

0.0392

AC XY:

1086

AN XY:

27688

show subpopulations

Gnomad AFR exome

AF:

0.0411

Gnomad AMR exome

AF:

0.0491

Gnomad ASJ exome

AF:

0.0423

Gnomad EAS exome

AF:

0.0854

Gnomad SAS exome

AF:

0.0319

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0388

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0414

AC:

48541

AN:

1171768

Hom.:

1146

Cov.:

AF XY:

0.0414

AC XY:

23797

AN XY:

575352

show subpopulations

Gnomad4 AFR exome

AF:

0.0535

Gnomad4 AMR exome

AF:

0.0528

Gnomad4 ASJ exome

AF:

0.0454

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.0335

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.0393

Gnomad4 OTH exome

AF:

0.0476

GnomAD4 genome

AF:

0.0505

AC:

7428

AN:

147120

Hom.:

220

Cov.:

AF XY:

0.0523

AC XY:

3745

AN XY:

71658

show subpopulations

Gnomad4 AFR

AF:

0.0559

Gnomad4 AMR

AF:

0.0505

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0419

Gnomad4 FIN

AF:

0.0630

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0216

Hom.:

Asia WGS

AF:

0.0630

AC:

168

AN:

2688

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2016	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. -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

DANN

Benign

0.35

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

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