Variant 1-228158286-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020435.4(GJC2):c.528G>A(p.Glu176=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 1,533,678 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00094 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 8 hom. )

Consequence

GJC2
NM_020435.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.948

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-228158286-G-A is Benign according to our data. Variant chr1-228158286-G-A is described in ClinVar as [Benign]. Clinvar id is 458297.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-228158286-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.948 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00094 (143/152124) while in subpopulation EAS AF= 0.0151 (78/5160). AF 95% confidence interval is 0.0124. There are 2 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJC2	NM_020435.4 linkuse as main transcript	c.528G>A	p.Glu176=	synonymous_variant	2/2	ENST00000366714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJC2	ENST00000366714.3 linkuse as main transcript	c.528G>A	p.Glu176=	synonymous_variant	2/2	1	NM_020435.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000921

AC:

140

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0145

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00172

AC:

236

AN:

137028

Hom.:

AF XY:

0.00178

AC XY:

133

AN XY:

74748

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.000285

Gnomad ASJ exome

AF:

0.000127

Gnomad EAS exome

AF:

0.0135

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00173

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.000725

GnomAD4 exome

AF:

0.000650

AC:

898

AN:

1381554

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

467

AN XY:

680844

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.000161

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.00190

Gnomad4 FIN exome

AF:

0.00184

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000923

GnomAD4 genome

AF:

0.000940

AC:

143

AN:

152124

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000518

Hom.:

Bravo

AF:

0.00105

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.60

DANN

Benign

0.32

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