NM_002063.4:c.717A>G

Variant names:

• chrX-14608992-A-G
• rs2090369987
• NM_002063.4:c.717A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_002063.4(GLRA2):​c.717A>G​(p.Gly239Gly) variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000078 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: GLRA2 NM_002063.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001511
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.116
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-14608992-A-G is Benign according to our data. Variant chrX-14608992-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3350603.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.116 with no splicing effect.

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.717A>G	p.Gly239Gly	splice_region synonymous	Exon 7 of 9	NP_002054.1	P23416-1
	GLRA2	NM_001118885.2		c.717A>G	p.Gly239Gly	splice_region synonymous	Exon 8 of 10	NP_001112357.1	P23416-1
	GLRA2	NM_001118886.2		c.717A>G	p.Gly239Gly	splice_region synonymous	Exon 7 of 9	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.717A>G	p.Gly239Gly	splice_region synonymous	Exon 7 of 9	ENSP00000218075.4	P23416-1
	GLRA2	ENST00000355020.9	TSL:1	c.717A>G	p.Gly239Gly	splice_region synonymous	Exon 7 of 9	ENSP00000347123.4	P23416-2
	GLRA2	ENST00000415367.2	TSL:3	n.968A>G		splice_region non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000776 AC: 7 AN: 901752 Hom.: 0 Cov.: 15 AF XY: 0.00000385 AC XY: 1 AN XY: 260048

African (AFR) AF: 0.00 AC: 0 AN: 22641

American (AMR) AF: 0.00 AC: 0 AN: 34564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18067

East Asian (EAS) AF: 0.00 AC: 0 AN: 29247

South Asian (SAS) AF: 0.00 AC: 0 AN: 49695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40391

Middle Eastern (MID) AF: 0.00163 AC: 6 AN: 3687

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 663953

Other (OTH) AF: 0.0000253 AC: 1 AN: 39507

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GLRA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.9
DANN	Benign	0.78
PhyloP100		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.026
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: rs2090369987; hg19: chrX-14627114;