rs7204714

Positions:

• chr16-23472032-C-A
• chr16-23472032-C-G
• chr16-23472032-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015044.4(GGA2):​c.1451-1867G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,044 control chromosomes in the GnomAD database, including 52,285 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 0.83 (52285 hom., cov: 30)
• Consequence: GGA2 NM_015044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGA2	NM_015044.4	c.1451-1867G>T		intron_variant		ENST00000309859.8	NP_055859.1
GGA2	XM_047433801.1	c.1421-1867G>T		intron_variant			XP_047289757.1
GGA2	XM_047433802.1	c.1340-1867G>T		intron_variant			XP_047289758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGA2	ENST00000309859.8	c.1451-1867G>T		intron_variant		1	NM_015044.4	ENSP00000311962.4
GGA2	ENST00000567468.5	c.625-6634G>T		intron_variant		2		ENSP00000454455.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125874 AN: 151926 Hom.: 52246 Cov.: 30

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.841

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.829 AC: 125969 AN: 152044 Hom.: 52285 Cov.: 30 AF XY: 0.825 AC XY: 61293 AN XY: 74324

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.836

Alfa AF: 0.836 Hom.: 49583

Bravo AF: 0.836

Asia WGS AF: 0.768 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.62
DANN	Benign	0.94

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

Other links and lift over

dbSNP: rs7204714; hg19: chr16-23483353;