rs1555999184

Variant names:

• chrX-14532376-G-A
• rs1555999184
• NM_002063.4:c.202+4G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-14532376-G-A
• chrX-14532376-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_002063.4(GLRA2):​c.202+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,038,542 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 2 hem.)
• Consequence: GLRA2 NM_002063.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004650
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 0 publications found

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]

GLRA2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked, syndromic, Pilorge type

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002063.4. 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
	GLRA2	NM_002063.4	MANE Select	c.202+4G>A		splice_region intron	N/A	NP_002054.1	P23416-1
	GLRA2	NM_001118885.2		c.202+4G>A		splice_region intron	N/A	NP_001112357.1	P23416-1
	GLRA2	NM_001118886.2		c.202+4G>A		splice_region intron	N/A	NP_001112358.1	P23416-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA2	ENST00000218075.9	TSL:1 MANE Select	c.202+4G>A		splice_region intron	N/A	ENSP00000218075.4	P23416-1
	GLRA2	ENST00000355020.9	TSL:1	c.202+4G>A		splice_region intron	N/A	ENSP00000347123.4	P23416-2
	GLRA2	ENST00000415367.2	TSL:3	n.453+4G>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000193 AC: 2 AN: 1038542 Hom.: 0 Cov.: 21 AF XY: 0.00000636 AC XY: 2 AN XY: 314594

African (AFR) AF: 0.00 AC: 0 AN: 24702

American (AMR) AF: 0.0000629 AC: 2 AN: 31772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17864

East Asian (EAS) AF: 0.00 AC: 0 AN: 29047

South Asian (SAS) AF: 0.00 AC: 0 AN: 46057

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39297

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3889

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 802319

Other (OTH) AF: 0.00 AC: 0 AN: 43595

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.50
PhyloP100		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000047
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.0		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: rs1555999184; hg19: chrX-14550498;