NM_002067.5:c.321+18T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002067.5(GNA11):​c.321+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,592,064 control chromosomes in the GnomAD database, including 164,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11806 hom., cov: 32)
  • Exomes 𝑓: 0.46 (152629 hom.)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-3110351-T-G is Benign according to our data. Variant chr19-3110351-T-G is described in ClinVar as Benign. ClinVar VariationId is 258546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	NM_002067.5	MANE Select	c.321+18T>G		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>G		intron	N/A	ENSP00000078429.3
	GNA11	ENST00000586763.1	TSL:3	n.140-2979T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57375 AN: 151190 Hom.: 11795 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.417 AC: 102212 AN: 244938 AF XY: 0.420

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.406

Gnomad FIN exome AF: 0.382

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.457 AC: 657747 AN: 1440758 Hom.: 152629 Cov.: 29 AF XY: 0.455 AC XY: 324903 AN XY: 713850

African (AFR) AF: 0.210 AC: 6826 AN: 32562

American (AMR) AF: 0.405 AC: 17945 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 9537 AN: 25878

East Asian (EAS) AF: 0.438 AC: 17168 AN: 39230

South Asian (SAS) AF: 0.403 AC: 34313 AN: 85048

European-Finnish (FIN) AF: 0.385 AC: 20344 AN: 52804

Middle Eastern (MID) AF: 0.375 AC: 2132 AN: 5682

European-Non Finnish (NFE) AF: 0.478 AC: 523378 AN: 1095968

Other (OTH) AF: 0.440 AC: 26104 AN: 59326

GnomAD4 genome AF: 0.379 AC: 57415 AN: 151306 Hom.: 11806 Cov.: 32 AF XY: 0.375 AC XY: 27756 AN XY: 73956

African (AFR) AF: 0.217 AC: 8853 AN: 40876

American (AMR) AF: 0.402 AC: 6133 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2096 AN: 5140

South Asian (SAS) AF: 0.398 AC: 1903 AN: 4786

European-Finnish (FIN) AF: 0.376 AC: 3967 AN: 10558

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32002 AN: 67914

Other (OTH) AF: 0.379 AC: 797 AN: 2104

Alfa AF: 0.394 Hom.: 4662

Bravo AF: 0.370

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.12
PhyloP100		-3.2
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: rs11085000; hg19: chr19-3110349; COSMIC: COSV50028098; COSMIC: COSV50028098;