chrX-14690691-G-GTC

Variant names:

• chrX-14690691-G-GTC
• rs752610633
• NM_002063.4:c.931-4_931-3dupTC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_Strong BS2

The NM_002063.4(GLRA2):​c.931-4_931-3dupTC variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000823 in 923,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000037 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000088 (0 hom. 4 hem.)
• Consequence: GLRA2 NM_002063.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

Genes affected

GLRA2 (HGNC:4327): (glycine receptor alpha 2) The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.11037528 fraction of the gene. Cryptic splice site detected, with MaxEntScore 14, offset of 0 (no position change), new splice context is: tctctctctctctctctcAGgtc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.931-4_931-3dupTC		splice_acceptor_variant, intron_variant	Intron 7 of 8	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.931-4_931-3dupTC		splice_acceptor_variant, intron_variant	Intron 7 of 8	1	NM_002063.4	ENSP00000218075.4

Frequencies

GnomAD3 genomes AF: 0.0000275 AC: 3 AN: 109126 Hom.: 0 Cov.: 23 AF XY: 0.0000314 AC XY: 1 AN XY: 31856

Gnomad AFR AF: 0.0000671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000285

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

GnomAD4 exome AF: 0.0000884 AC: 72 AN: 814788 Hom.: 0 Cov.: 15 AF XY: 0.0000168 AC XY: 4 AN XY: 237594

Gnomad4 AFR exome AF: 0.000439

Gnomad4 AMR exome AF: 0.0000978

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000387

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000959

Gnomad4 OTH exome AF: 0.0000284

GnomAD4 genome AF: 0.0000366 AC: 4 AN: 109169 Hom.: 0 Cov.: 23 AF XY: 0.0000313 AC XY: 1 AN XY: 31909

Gnomad4 AFR AF: 0.0000670

Gnomad4 AMR AF: 0.0000978

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000286

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs752610633; hg19: chrX-14708813;