19-3094599-GGGGGCCGGGGGGCGGCGGCGGGCAGGCGGCCGCGTCGGCC-G

Position:

• chr19-3094599-GGGGGCCGGGGGGCGGCGGCGGGCAGGCGGCCGCGTCGGCC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002067.5(GNA11):​c.-43_-4del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 146,432 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0069 (21 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNA11 NM_002067.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 19-3094599-GGGGGCCGGGGGGCGGCGGCGGGCAGGCGGCCGCGTCGGCC-G is Benign according to our data. Variant chr19-3094599-GGGGGCCGGGGGGCGGCGGCGGGCAGGCGGCCGCGTCGGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1211124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3094599-GGGGGCCGGGGGGCGGCGGCGGGCAGGCGGCCGCGTCGGCC-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00388 (568/146432) while in subpopulation NFE AF= 0.00624 (412/66060). AF 95% confidence interval is 0.00574. There are 2 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 568 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA11	NM_002067.5	c.-43_-4del		5_prime_UTR_variant	1/7	ENST00000078429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA11	ENST00000078429.9	c.-43_-4del		5_prime_UTR_variant	1/7	1	NM_002067.5	P1
GNA11	ENST00000586763.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 568 AN: 146386 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00318

Gnomad ASJ AF: 0.00587

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.00212

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.00624

Gnomad OTH AF: 0.00547

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00694 AC: 5585 AN: 805008 Hom.: 21 AF XY: 0.00715 AC XY: 2687 AN XY: 376008

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.000534

Gnomad4 SAS exome AF: 0.00350

Gnomad4 FIN exome AF: 0.00975

Gnomad4 NFE exome AF: 0.00705

Gnomad4 OTH exome AF: 0.00723

GnomAD4 genome AF: 0.00388 AC: 568 AN: 146432 Hom.: 2 Cov.: 31 AF XY: 0.00327 AC XY: 233 AN XY: 71270

Gnomad4 AFR AF: 0.00121

Gnomad4 AMR AF: 0.00318

Gnomad4 ASJ AF: 0.00587

Gnomad4 EAS AF: 0.00119

Gnomad4 SAS AF: 0.000628

Gnomad4 FIN AF: 0.00212

Gnomad4 NFE AF: 0.00624

Gnomad4 OTH AF: 0.00542

Alfa AF: 0.00557 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs571847017; hg19: chr19-3094597;