Genetic Variant NM_002063.4:c.1080+11680T>G (chrX-14702539-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002063.4(GLRA2):c.1080+11680T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 111,916 control chromosomes in the GnomAD database, including 524 homozygotes. There are 2,544 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.081 ( 524 hom., 2544 hem., cov: 23)

Consequence

GLRA2
NM_002063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.357

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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
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

FANCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA2	NM_002063.4 link	c.1080+11680T>G		intron_variant	Intron 8 of 8	ENST00000218075.9	NP_002054.1	P23416-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9 link	c.1080+11680T>G		intron_variant	Intron 8 of 8	1	NM_002063.4	ENSP00000218075.4		P23416-1

Frequencies

GnomAD3 genomes

AF:

0.0814

AC:

9108

AN:

111864

Hom.:

527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0211

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0389

Gnomad FIN

AF:

0.00737

Gnomad MID

AF:

0.0295

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0703

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0814

AC:

9108

AN:

111916

Hom.:

524

Cov.:

AF XY:

0.0746

AC XY:

2544

AN XY:

34092

show subpopulations

African (AFR)

AF:

0.190

AC:

5836

AN:

30697

American (AMR)

AF:

0.125

AC:

1316

AN:

10537

Ashkenazi Jewish (ASJ)

AF:

0.0211

AC:

AN:

2651

East Asian (EAS)

AF:

0.141

AC:

500

AN:

3545

South Asian (SAS)

AF:

0.0393

AC:

106

AN:

2694

European-Finnish (FIN)

AF:

0.00737

AC:

AN:

6109

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0213

AC:

1137

AN:

53256

Other (OTH)

AF:

0.0694

AC:

106

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

280

560

839

1119

1399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0581

Hom.:

816

Bravo

AF:

0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.37

(source)

DANN

Benign

0.88

PhyloP100

-0.36

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over