1-228157753-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_020435.4(GJC2):c.-6G>C variant causes a 5 prime UTR change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (0 hom., cov: 0)
  • Exomes 𝑓: 0.18 (489 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJC2 NM_020435.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 1-228157753-G-C is Benign according to our data. Variant chr1-228157753-G-C is described in ClinVar as [Benign]. Clinvar id is 402902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 38 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJC2	NM_020435.4	c.-6G>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.-6G>C		5_prime_UTR_variant	2/2	1	NM_020435.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9189 AN: 30906 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.446 AC: 36862 AN: 82652 Hom.: 38 AF XY: 0.446 AC XY: 19544 AN XY: 43866

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.490

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.468

Gnomad SAS exome AF: 0.440

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.458

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.180 AC: 98728 AN: 549468 Hom.: 489 Cov.: 19 AF XY: 0.192 AC XY: 53456 AN XY: 278490

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.297 AC: 9189 AN: 30890 Hom.: 0 Cov.: 0 AF XY: 0.271 AC XY: 4186 AN XY: 15474

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.304

Alfa AF: 0.00159 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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	-0.36
Cadd	Benign	19
Dann	Benign	0.83

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: rs762585789; hg19: chr1-228345454;