Variant chr16-23470016-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015044.4(GGA2):c.1600T>C(p.Phe534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,409,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

GGA2
NM_015044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

Variant links:

Genes affected

GGA2 (HGNC:16064): (golgi associated, gamma adaptin ear containing, ARF binding protein 2) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]

GGA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GGA2	NM_015044.4 linkuse as main transcript	c.1600T>C	p.Phe534Leu	missense_variant	15/17	ENST00000309859.8
GGA2	XM_047433801.1 linkuse as main transcript	c.1570T>C	p.Phe524Leu	missense_variant	16/18
GGA2	XM_047433802.1 linkuse as main transcript	c.1489T>C	p.Phe497Leu	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGA2	ENST00000309859.8 linkuse as main transcript	c.1600T>C	p.Phe534Leu	missense_variant	15/17	1	NM_015044.4	P1
GGA2	ENST00000567468.5 linkuse as main transcript	c.625-4618T>C		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000916

AC:

AN:

218386

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

118714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000497

AC:

AN:

1409124

Hom.:

Cov.:

AF XY:

0.00000717

AC XY:

AN XY:

697532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000645

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000314

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.1600T>C (p.F534L) alteration is located in exon 15 (coding exon 15) of the GGA2 gene. This alteration results from a T to C substitution at nucleotide position 1600, causing the phenylalanine (F) at amino acid position 534 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.90

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.20

Sift

Benign

0.36

Sift4G

Benign

0.39

Polyphen

0.84

Vest4

0.47

MutPred

0.79

Gain of disorder (P = 0.0876);

MVP

0.41

MPC

0.26

ClinPred

0.64

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.62

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