Genetic Variant NM_002067.5:c.*2458C>T (chr19-3123637-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002067.5(GNA11):c.*2458C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 232,848 control chromosomes in the GnomAD database, including 11,571 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 0.31 ( 7495 hom., cov: 33)

Exomes 𝑓: 0.31 ( 4076 hom. )

Consequence

GNA11
NM_002067.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.241

Publications

4 publications found

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 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

GNA11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA11	NM_002067.5 link	c.*2458C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000078429.9	NP_002058.2	P29992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9 link	c.*2458C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_002067.5	ENSP00000078429.3		P29992

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46385

AN:

151934

Hom.:

7491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.321

GnomAD4 exome

AF:

0.309

AC:

24969

AN:

80796

Hom.:

4076

Cov.:

AF XY:

0.311

AC XY:

11559

AN XY:

37142

show subpopulations

African (AFR)

AF:

0.226

AC:

878

AN:

3884

American (AMR)

AF:

0.239

AC:

596

AN:

2496

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1911

AN:

5112

East Asian (EAS)

AF:

0.187

AC:

2127

AN:

11392

South Asian (SAS)

AF:

0.148

AC:

104

AN:

704

European-Finnish (FIN)

AF:

0.483

AC:

AN:

Middle Eastern (MID)

AF:

0.336

AC:

166

AN:

494

European-Non Finnish (NFE)

AF:

0.342

AC:

17044

AN:

49898

Other (OTH)

AF:

0.313

AC:

2115

AN:

6758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

964

1928

2892

3856

4820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.305

AC:

46398

AN:

152052

Hom.:

7495

Cov.:

AF XY:

0.305

AC XY:

22668

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.240

AC:

9956

AN:

41456

American (AMR)

AF:

0.256

AC:

3908

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1305

AN:

3468

East Asian (EAS)

AF:

0.194

AC:

997

AN:

5150

South Asian (SAS)

AF:

0.182

AC:

880

AN:

4826

European-Finnish (FIN)

AF:

0.434

AC:

4594

AN:

10584

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23612

AN:

67960

Other (OTH)

AF:

0.317

AC:

671

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1626

3253

4879

6506

8132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.319

Hom.:

4184

Bravo

AF:

0.293

Asia WGS

AF:

0.169

AC:

592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.0

(source)

DANN

Benign

0.70

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over