rs11085000

Variant names:

• chr19-3110351-T-A
• rs11085000
• NM_002067.5:c.321+18T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3110351-T-A
• chr19-3110351-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002067.5(GNA11):​c.321+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000763 in 1,442,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.24
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-3110351-T-A is Benign according to our data. Variant chr19-3110351-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2999828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 11 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	NM_002067.5	MANE Select	c.321+18T>A		intron	N/A	NP_002058.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	ENST00000078429.9	TSL:1 MANE Select	c.321+18T>A		intron	N/A	ENSP00000078429.3
	GNA11	ENST00000586763.1	TSL:3	n.140-2979T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 244938 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000763 AC: 11 AN: 1442460 Hom.: 0 Cov.: 29 AF XY: 0.00000980 AC XY: 7 AN XY: 714648

African (AFR) AF: 0.00 AC: 0 AN: 32594

American (AMR) AF: 0.0000226 AC: 1 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25894

East Asian (EAS) AF: 0.0000764 AC: 3 AN: 39244

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85100

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1097424

Other (OTH) AF: 0.00 AC: 0 AN: 59384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4662

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.19
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11085000; hg19: chr19-3110349;