Genetic Variant GLRA2:c.931-8_931-3delTCTCTC (chrX-14690691-GTCTCTC-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002063.4(GLRA2):c.931-8_931-3delTCTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 815,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000012 ( 0 hom. 1 hem. )

Consequence

GLRA2
NM_002063.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

0 publications found

Variant links:

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 links:

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]

FANCB Gene-Disease associations (from GenCC):

Fanconi anemia complementation group B
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
VACTERL association, X-linked, with or without hydrocephalus
Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
VACTERL with hydrocephalus
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

FANCB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLRA2	NM_002063.4	MANE Select	c.931-8_931-3delTCTCTC	splice_region intron	N/A	NP_002054.1	P23416-1
GLRA2	NM_001118885.2		c.931-8_931-3delTCTCTC	splice_region intron	N/A	NP_001112357.1	P23416-1
GLRA2	NM_001118886.2		c.931-8_931-3delTCTCTC	splice_region intron	N/A	NP_001112358.1	P23416-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLRA2	ENST00000218075.9	TSL:1 MANE Select	c.931-8_931-3delTCTCTC	splice_region intron	N/A	ENSP00000218075.4	P23416-1
GLRA2	ENST00000355020.9	TSL:1	c.931-8_931-3delTCTCTC	splice_region intron	N/A	ENSP00000347123.4	P23416-2
FANCB	ENST00000696351.1		n.925_930delGAGAGA	non_coding_transcript_exon	Exon 15 of 15	ENSP00000512572.1	A0A8Q3SJA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000123

AC:

AN:

815649

Hom.:

AF XY:

0.00000420

AC XY:

AN XY:

237971

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20510

American (AMR)

AF:

0.00

AC:

AN:

30669

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15565

East Asian (EAS)

AF:

0.00

AC:

AN:

25853

South Asian (SAS)

AF:

0.00

AC:

AN:

43335

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35517

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3198

European-Non Finnish (NFE)

AF:

0.00000165

AC:

AN:

605788

Other (OTH)

AF:

0.00

AC:

AN:

35214

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over