Genetic Variant GJC2:c.-14G>A (chr1-228157745-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020435.4(GJC2):c.-14G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 718,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000017 ( 1 hom. )

Consequence

GJC2
NM_020435.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
lymphatic malformation 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia 44
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
lymphatic malformation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GJC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020435.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJC2	NM_020435.4	MANE Select	c.-14G>A		5_prime_UTR	Exon 2 of 2	NP_065168.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJC2	ENST00000366714.3	TSL:1 MANE Select	c.-14G>A	5_prime_UTR	Exon 2 of 2	ENSP00000355675.2	Q5T442
GJC2	ENST00000886860.1		c.-14G>A	5_prime_UTR	Exon 2 of 2	ENSP00000556919.1
GJC2	ENST00000963922.1		c.-14G>A	5_prime_UTR	Exon 2 of 2	ENSP00000633981.1

Frequencies

GnomAD3 genomes

AF:

0.0000186

AC:

AN:

53778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000167

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

83214

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000135

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

664782

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

340160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17478

American (AMR)

AF:

0.000222

AC:

AN:

26978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17514

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30256

South Asian (SAS)

AF:

0.00

AC:

AN:

51872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2522

European-Non Finnish (NFE)

AF:

0.00000884

AC:

AN:

452340

Other (OTH)

AF:

0.00

AC:

AN:

32506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000186

AC:

AN:

53778

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

26570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12882

American (AMR)

AF:

0.000167

AC:

AN:

5982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1278

East Asian (EAS)

AF:

0.00

AC:

AN:

2128

South Asian (SAS)

AF:

0.00

AC:

AN:

1810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4490

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

24198

Other (OTH)

AF:

0.00

AC:

AN:

704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.0

(source)

DANN

Benign

0.78

PhyloP100

-0.28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over