rs2126986

Variant names:

• chr16-56317795-A-G
• rs2126986
• NM_020988.3:c.304-10836A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-56317795-A-G
• chr16-56317795-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020988.3(GNAO1):​c.304-10836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,858 control chromosomes in the GnomAD database, including 19,739 homozygotes. 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 0.50 (19739 hom., cov: 31)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 7 publications found

Genes affected

GNAO1 (HGNC:4389): (G protein subunit alpha o1) The protein encoded by this gene represents the alpha subunit of the Go heterotrimeric G-protein signal-transducing complex. Defects in this gene are a cause of early-onset epileptic encephalopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

GNAO1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• movement disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• neurodevelopmental disorder with involuntary movements

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.304-10836A>G		intron_variant	Intron 3 of 8	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.304-10836A>G		intron_variant	Intron 3 of 7		NP_620073.2
GNAO1	XM_011523003.4	c.178-10836A>G		intron_variant	Intron 3 of 8		XP_011521305.1
GNAO1	XR_007064866.1	n.1051-10836A>G		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.304-10836A>G		intron_variant	Intron 3 of 8	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75784 AN: 151740 Hom.: 19730 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.499 AC: 75826 AN: 151858 Hom.: 19739 Cov.: 31 AF XY: 0.490 AC XY: 36357 AN XY: 74170

African (AFR) AF: 0.628 AC: 26003 AN: 41384

American (AMR) AF: 0.411 AC: 6271 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1704 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1283 AN: 5152

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4816

European-Finnish (FIN) AF: 0.383 AC: 4047 AN: 10554

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32346 AN: 67898

Other (OTH) AF: 0.484 AC: 1021 AN: 2110

Alfa AF: 0.480 Hom.: 71987

Bravo AF: 0.508

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2126986; hg19: chr16-56351707;