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

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.24

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 258546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3110351-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA11	NM_002067.5 link	c.321+18T>G		intron_variant	Intron 2 of 6	ENST00000078429.9	NP_002058.2	P29992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9 link	c.321+18T>G		intron_variant	Intron 2 of 6	1	NM_002067.5	ENSP00000078429.3		P29992
GNA11	ENST00000586763.1 link	n.140-2979T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57375

AN:

151190

Hom.:

11795

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.417

AC:

102212

AN:

244938

Hom.:

21944

AF XY:

0.420

AC XY:

55899

AN XY:

133138

show subpopulations

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 SAS exome

AF:

0.404

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.:

AF XY:

0.455

AC XY:

324903

AN XY:

713850

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.379

AC:

57415

AN:

151306

Hom.:

11806

Cov.:

AF XY:

0.375

AC XY:

27756

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.408

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.376

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.378

Hom.:

2387

Bravo

AF:

0.370

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 29, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.40

DANN

Benign

0.12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over