1-228158352-C-T

Position:

chr1-228158352-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020435.4(GJC2):c.594C>T(p.His198His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,588,150 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 68 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1263 hom. )

Consequence

GJC2
NM_020435.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.273

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=-0.51).

BP6

Variant 1-228158352-C-T is Benign according to our data. Variant chr1-228158352-C-T is described in ClinVar as [Benign]. Clinvar id is 241298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-228158352-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.273 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3808/151878) while in subpopulation NFE AF= 0.0417 (2834/67902). AF 95% confidence interval is 0.0405. There are 68 homozygotes in gnomad4. There are 1761 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 68 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC2	NM_020435.4 linkuse as main transcript	c.594C>T	p.His198His	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.594C>T	p.His198His	synonymous_variant	2/2	1	NM_020435.4	ENSP00000355675.2		Q5T442

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3813

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00717

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0289

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0294

AC:

6109

AN:

207860

Hom.:

147

AF XY:

0.0313

AC XY:

3583

AN XY:

114606

show subpopulations

Gnomad AFR exome

AF:

0.00642

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.000256

Gnomad SAS exome

AF:

0.0431

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0418

Gnomad OTH exome

AF:

0.0305

GnomAD4 exome

AF:

0.0393

AC:

56385

AN:

1436272

Hom.:

1263

Cov.:

AF XY:

0.0396

AC XY:

28255

AN XY:

713512

show subpopulations

Gnomad4 AFR exome

AF:

0.00499

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0438

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0438

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0251

AC:

3808

AN:

151878

Hom.:

Cov.:

AF XY:

0.0237

AC XY:

1761

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00715

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.0289

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0383

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0417

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0343

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.0160

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 26, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 20, 2022

- -

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

-0.51

CADD

Benign

8.5

DANN

Benign

0.60

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