Genetic Variant GNG2:p.Leu51Met (chr14-51966622-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_053064.5(GNG2):c.151C>A(p.Leu51Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,613,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

GNG2
NM_053064.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

2 publications found

Variant links:

Genes affected

GNG2 (HGNC:4404): (G protein subunit gamma 2) This gene encodes one of the gamma subunits of a guanine nucleotide-binding protein. Such proteins are involved in signaling mechanisms across membranes. Various subunits forms heterodimers which then interact with the different signal molecules. [provided by RefSeq, Aug 2011]

GNG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21466854).

BS2

High AC in GnomAd4 at 21 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053064.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNG2	NM_053064.5	MANE Select	c.151C>A	p.Leu51Met	missense	Exon 4 of 4	NP_444292.1	P59768
GNG2	NM_001243773.2		c.151C>A	p.Leu51Met	missense	Exon 4 of 4	NP_001230702.1	P59768
GNG2	NM_001243774.2		c.151C>A	p.Leu51Met	missense	Exon 3 of 3	NP_001230703.1	P59768

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNG2	ENST00000556766.6	TSL:1 MANE Select	c.151C>A	p.Leu51Met	missense	Exon 4 of 4	ENSP00000451231.1	P59768
GNG2	ENST00000556752.2	TSL:1	c.151C>A	p.Leu51Met	missense	Exon 3 of 3	ENSP00000451576.1	P59768
GNG2	ENST00000553299.5	TSL:1	n.1124C>A		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

251332

AF XY:

0.000155

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1461118

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33474

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000255

AC:

283

AN:

1111316

Other (OTH)

AF:

0.000232

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000138

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41440

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000268

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

M_CAP

Benign

0.032

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

PhyloP100

1.2

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.029

Polyphen

0.88

Vest4

0.40

MVP

0.29

MPC

2.0

ClinPred

0.35

GERP RS

3.1

Varity_R

0.65

gMVP

0.72

Mutation Taster

=61/39

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over