16-75566505-G-A

Variant names:

• chr16-75566505-G-A
• NM_007285.7:c.19G>A

Variant summary

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

The NM_007285.7(GABARAPL2):​c.19G>A​(p.Glu7Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GABARAPL2 NM_007285.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85

Genes affected

GABARAPL2 (HGNC:13291): (GABA type A receptor associated protein like 2) Enables ubiquitin protein ligase binding activity. Involved in negative regulation of proteasomal protein catabolic process and protein localization to endoplasmic reticulum. Located in Golgi membrane and autophagosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259992 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
GABARAPL2	NM_007285.7	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 4	ENST00000037243.7	NP_009216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABARAPL2	ENST00000037243.7	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 4	1	NM_007285.7	ENSP00000037243.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>A (p.E7K) alteration is located in exon 1 (coding exon 1) of the GABARAPL2 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a lysine (K). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-0.052
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.1	N;N;D
REVEL	Benign	0.21
Sift	Benign	0.18	T;T;D
Sift4G	Benign	0.24	T;T;D
Polyphen		0.0020	B;.;.
Vest4		0.73
MutPred		0.40		Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);
MVP		0.52
MPC		0.99
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.76
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75600403;