1-228157700-TAAGTGCAGGCCCCTGGC-T

Position:

• chr1-228157700-TAAGTGCAGGCCCCTGGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020435.4(GJC2):​c.-19-39_-19-23del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,296,562 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: GJC2 NM_020435.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.613

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 -10 ACMG points.

• BP6: Variant 1-228157700-TAAGTGCAGGCCCCTGGC-T is Benign according to our data. Variant chr1-228157700-TAAGTGCAGGCCCCTGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1684100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00281 (427/152192) while in subpopulation AFR AF= 0.00995 (413/41524). AF 95% confidence interval is 0.00915. There are 5 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC2	NM_020435.4	c.-19-39_-19-23del		intron_variant		ENST00000366714.3	NP_065168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC2	ENST00000366714.3	c.-19-39_-19-23del		intron_variant		1	NM_020435.4	ENSP00000355675	P1

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 421 AN: 152074 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00983

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000142 AC: 162 AN: 1144370 Hom.: 1 AF XY: 0.000111 AC XY: 63 AN XY: 569754

Gnomad4 AFR exome AF: 0.00508

Gnomad4 AMR exome AF: 0.000474

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000115

Gnomad4 OTH exome AF: 0.000224

GnomAD4 genome AF: 0.00281 AC: 427 AN: 152192 Hom.: 5 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74406

Gnomad4 AFR AF: 0.00995

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00171 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs577811454; hg19: chr1-228345401;