9-77728669-T-TG

Variant names:

• chr9-77728669-T-TG
• rs757232284
• NM_002072.5:c.736-3dupC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_002072.5(GNAQ):​c.736-3dupC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000165 in 1,457,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.49
• Publications: 1 publications found

Genes affected

GNAQ (HGNC:4390): (G protein subunit alpha q) This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

GNAQ Gene-Disease associations (from GenCC):

• congenital hemangioma

  Inheritance: AD Classification: STRONG Submitted by: G2P
• Sturge-Weber syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 9-77728669-T-TG is Benign according to our data. Variant chr9-77728669-T-TG is described in ClinVar as Likely_benign. ClinVar VariationId is 3058149.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	NM_002072.5	MANE Select	c.736-3dupC		splice_region intron	N/A	NP_002063.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	ENST00000286548.9	TSL:1 MANE Select	c.736-3dupC		splice_region intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.811-3dupC		splice_region intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.736-3dupC		splice_region intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 12 AN: 86358 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000356

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: 0.000288

Gnomad OTH AF: 0.000887

GnomAD2 exomes AF: 0.0000666 AC: 12 AN: 180240 AF XY: 0.0000605

Gnomad AFR exome AF: 0.000143

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 229 AN: 1371404 Hom.: 0 Cov.: 26 AF XY: 0.000164 AC XY: 112 AN XY: 683076

African (AFR) AF: 0.000201 AC: 6 AN: 29902

American (AMR) AF: 0.0000306 AC: 1 AN: 32694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23828

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38978

South Asian (SAS) AF: 0.0000514 AC: 4 AN: 77752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.000187 AC: 198 AN: 1056138

Other (OTH) AF: 0.000335 AC: 19 AN: 56674

GnomAD4 genome AF: 0.000139 AC: 12 AN: 86462 Hom.: 0 Cov.: 30 AF XY: 0.000189 AC XY: 8 AN XY: 42370

African (AFR) AF: 0.0000355 AC: 1 AN: 28190

American (AMR) AF: 0.00 AC: 0 AN: 7712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1972

East Asian (EAS) AF: 0.00 AC: 0 AN: 4072

South Asian (SAS) AF: 0.00 AC: 0 AN: 2872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.000288 AC: 10 AN: 34742

Other (OTH) AF: 0.000876 AC: 1 AN: 1142

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GNAQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=72/28	polymorphism

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: rs757232284; hg19: chr9-80343585;