Genetic Variant GLRA2:p.Ala108Ala (chrX-14581236-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_002063.4(GLRA2):c.324G>A(p.Ala108Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,187,078 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000020 ( 0 hom. 9 hem. )

Consequence

GLRA2
NM_002063.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0720

Publications

2 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 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked, syndromic, Pilorge type
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GLRA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant X-14581236-G-A is Benign according to our data. Variant chrX-14581236-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3039889.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.072 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRA2	NM_002063.4	MANE Select	c.324G>A	p.Ala108Ala	synonymous	Exon 4 of 9	NP_002054.1	P23416-1
GLRA2	NM_001118885.2		c.324G>A	p.Ala108Ala	synonymous	Exon 5 of 10	NP_001112357.1	P23416-1
GLRA2	NM_001118886.2		c.324G>A	p.Ala108Ala	synonymous	Exon 4 of 9	NP_001112358.1	P23416-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRA2	ENST00000218075.9	TSL:1 MANE Select	c.324G>A	p.Ala108Ala	synonymous	Exon 4 of 9	ENSP00000218075.4	P23416-1
GLRA2	ENST00000355020.9	TSL:1	c.324G>A	p.Ala108Ala	synonymous	Exon 4 of 9	ENSP00000347123.4	P23416-2
GLRA2	ENST00000415367.2	TSL:3	n.575G>A		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000437

AC:

AN:

183178

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1075505

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

342651

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26007

American (AMR)

AF:

0.0000853

AC:

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19242

East Asian (EAS)

AF:

0.0000996

AC:

AN:

30135

South Asian (SAS)

AF:

0.0000746

AC:

AN:

53611

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

821377

Other (OTH)

AF:

0.0000221

AC:

AN:

45329

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111573

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33757

show subpopulations

African (AFR)

AF:

0.0000978

AC:

AN:

30680

American (AMR)

AF:

0.00

AC:

AN:

10502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3543

South Asian (SAS)

AF:

0.00

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53134

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GLRA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.4

(source)

DANN

Benign

0.70

PhyloP100

0.072

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over