rs308062

Variant names:

• chr19-3112006-A-G
• rs308062
• NM_002067.5:c.322-1324A>G

Variant summary

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

The NM_002067.5(GNA11):​c.322-1324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,270 control chromosomes in the GnomAD database, including 61,133 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 0.89 (61133 hom., cov: 34)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 3 publications found

Genes affected

GNA11 (HGNC:4379): (G protein subunit alpha 11) The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

GNA11 Gene-Disease associations (from GenCC):

• autosomal dominant hypocalcemia 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• congenital hemangioma

  Inheritance: AD Classification: STRONG Submitted by: G2P
• familial hypocalciuric hypercalcemia 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet
• autosomal dominant hypocalcemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002067.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	NM_002067.5	MANE Select	c.322-1324A>G		intron	N/A	NP_002058.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	ENST00000078429.9	TSL:1 MANE Select	c.322-1324A>G		intron	N/A	ENSP00000078429.3
	GNA11	ENST00000586763.1	TSL:3	n.140-1324A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.894 AC: 136012 AN: 152152 Hom.: 61072 Cov.: 34

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.894 AC: 136132 AN: 152270 Hom.: 61133 Cov.: 34 AF XY: 0.890 AC XY: 66273 AN XY: 74452

African (AFR) AF: 0.975 AC: 40548 AN: 41580

American (AMR) AF: 0.911 AC: 13929 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2988 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4011 AN: 5172

South Asian (SAS) AF: 0.753 AC: 3634 AN: 4824

European-Finnish (FIN) AF: 0.873 AC: 9259 AN: 10610

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 58996 AN: 68000

Other (OTH) AF: 0.887 AC: 1876 AN: 2116

Alfa AF: 0.894 Hom.: 9871

Bravo AF: 0.903

Asia WGS AF: 0.795 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.32
PhyloP100		-1.4
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: rs308062; hg19: chr19-3112004;