rs2238625

Variant names:

• chr19-3104654-T-C
• rs2238625
• NM_002067.5:c.137-5495T>C

Variant summary

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

The NM_002067.5(GNA11):​c.137-5495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,016 control chromosomes in the GnomAD database, including 21,645 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 0.52 (21645 hom., cov: 33)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 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.137-5495T>C		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.137-5495T>C		intron	N/A	ENSP00000078429.3
	GNA11	ENST00000586763.1	TSL:3	n.140-8676T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78383 AN: 151898 Hom.: 21617 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.516 AC: 78452 AN: 152016 Hom.: 21645 Cov.: 33 AF XY: 0.517 AC XY: 38425 AN XY: 74314

African (AFR) AF: 0.712 AC: 29512 AN: 41450

American (AMR) AF: 0.525 AC: 8021 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2037 AN: 5136

South Asian (SAS) AF: 0.399 AC: 1920 AN: 4816

European-Finnish (FIN) AF: 0.512 AC: 5412 AN: 10568

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28184 AN: 67976

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.455 Hom.: 49101

Bravo AF: 0.530

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.30
PhyloP100		-3.9
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: rs2238625; hg19: chr19-3104652;