Variant chr16-23467604-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015044.4(GGA2):c.1828T>G(p.Leu610Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GGA2
NM_015044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.100

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20241347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GGA2	NM_015044.4 linkuse as main transcript	c.1828T>G	p.Leu610Val	missense_variant	17/17	ENST00000309859.8
GGA2	XM_047433801.1 linkuse as main transcript	c.1798T>G	p.Leu600Val	missense_variant	18/18
GGA2	XM_047433802.1 linkuse as main transcript	c.1717T>G	p.Leu573Val	missense_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GGA2	ENST00000309859.8 linkuse as main transcript	c.1828T>G	p.Leu610Val	missense_variant	17/17	1	NM_015044.4	P1
GGA2	ENST00000567468.5 linkuse as main transcript	c.625-2206T>G		intron_variant		2
GGA2	ENST00000568922.1 linkuse as main transcript	n.794T>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247334

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1421070

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jun 10, 2022

The c.1828T>G (p.L610V) alteration is located in exon 17 (coding exon 17) of the GGA2 gene. This alteration results from a T to G substitution at nucleotide position 1828, causing the leucine (L) at amino acid position 610 to be replaced by a valine (V). 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

Benign

0.081

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.73

REVEL

Benign

0.12

Sift

Benign

0.089

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.094

MutPred

0.50

Gain of catalytic residue at L610 (P = 0.0292);

MVP

0.67

MPC

0.55

ClinPred

0.52

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.32

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