dbSNP rs78179793: GLRA2:p.Asp363Asp (chrX-14730215-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002063.4(GLRA2):c.1089C>T(p.Asp363Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,197,288 control chromosomes in the GnomAD database, including 74 homozygotes. There are 1,003 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 40 hom., 509 hem., cov: 22)

Exomes 𝑓: 0.0019 ( 34 hom. 494 hem. )

Consequence

GLRA2
NM_002063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.585

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-14730215-C-T is Benign according to our data. Variant chrX-14730215-C-T is described in ClinVar as Benign. ClinVar VariationId is 780683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.585 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

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.1089C>T	p.Asp363Asp	synonymous	Exon 9 of 9	NP_002054.1	P23416-1
GLRA2	NM_001118885.2		c.1089C>T	p.Asp363Asp	synonymous	Exon 10 of 10	NP_001112357.1	P23416-1
GLRA2	NM_001118886.2		c.1089C>T	p.Asp363Asp	synonymous	Exon 9 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.1089C>T	p.Asp363Asp	synonymous	Exon 9 of 9	ENSP00000218075.4	P23416-1
GLRA2	ENST00000355020.9	TSL:1	c.1089C>T	p.Asp363Asp	synonymous	Exon 9 of 9	ENSP00000347123.4	P23416-2
GLRA2	ENST00000415367.2	TSL:3	n.1340C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

1999

AN:

111172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00847

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.0149

GnomAD2 exomes

AF:

0.00530

AC:

966

AN:

182206

AF XY:

0.00341

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.00369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00400

GnomAD4 exome

AF:

0.00186

AC:

2018

AN:

1086065

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

494

AN XY:

352643

show subpopulations

African (AFR)

AF:

0.0580

AC:

1517

AN:

26139

American (AMR)

AF:

0.00498

AC:

175

AN:

35149

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19284

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30146

South Asian (SAS)

AF:

0.0000558

AC:

AN:

53792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40501

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

4111

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

831261

Other (OTH)

AF:

0.00468

AC:

214

AN:

45682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0180

AC:

1999

AN:

111223

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

509

AN XY:

33445

show subpopulations

African (AFR)

AF:

0.0604

AC:

1848

AN:

30595

American (AMR)

AF:

0.0112

AC:

117

AN:

10406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2635

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5922

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000188

AC:

AN:

53111

Other (OTH)

AF:

0.0147

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

129

193

258

322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0113

Hom.:

Bravo

AF:

0.0216

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000595

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GLRA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.97

(source)

DANN

Benign

0.72

PhyloP100

-0.58

Mutation Taster

=97/3

polymorphism (auto)

(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