1-228157749-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_020435.4(GJC2):c.-10G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (1071 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJC2 NM_020435.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-228157749-G-C is Benign according to our data. Variant chr1-228157749-G-C is described in ClinVar as [Benign]. Clinvar id is 1175616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 47 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJC2	NM_020435.4	c.-10G>C		5_prime_UTR_variant	2/2	ENST00000366714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJC2	ENST00000366714.3	c.-10G>C		5_prime_UTR_variant	2/2	1	NM_020435.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9952 AN: 40500 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.274

GnomAD3 exomes AF: 0.478 AC: 39578 AN: 82722 Hom.: 47 AF XY: 0.481 AC XY: 21243 AN XY: 44190

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.494

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.475

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.472

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.123 AC: 102212 AN: 833230 Hom.: 1071 Cov.: 22 AF XY: 0.133 AC XY: 55560 AN XY: 417718

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.0815

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.246 AC: 9953 AN: 40466 Hom.: 0 Cov.: 0 AF XY: 0.226 AC XY: 4555 AN XY: 20198

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.274

Alfa AF: 0.00107 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.44
Cadd	Benign	14
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs769532107; hg19: chr1-228345450;