rs75469429

Variant names:

• chr1-228157866-C-A
• rs75469429
• NM_020435.4:c.108C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-228157866-C-A
• chr1-228157866-C-G
• chr1-228157866-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020435.4(GJC2):​c.108C>A​(p.Ile36Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I36I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJC2 NM_020435.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 5 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• lymphatic malformation 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.

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.108C>A	p.Ile36Ile	synonymous	Exon 2 of 2	NP_065168.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJC2	ENST00000366714.3	TSL:1 MANE Select	c.108C>A	p.Ile36Ile	synonymous	Exon 2 of 2	ENSP00000355675.2
	GJC2	ENST00000886860.1		c.108C>A	p.Ile36Ile	synonymous	Exon 2 of 2	ENSP00000556919.1
	GJC2	ENST00000963922.1		c.108C>A	p.Ile36Ile	synonymous	Exon 2 of 2	ENSP00000633981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 244924 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459296 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 725768

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111412

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs75469429; hg19: chr1-228345567;