NM_001667.4:c.442C>G

Variant names:

• chr11-65021742-C-G
• rs375384323
• NM_001667.4:c.442C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001667.4(ARL2):​c.442C>G​(p.Arg148Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,454,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ARL2 NM_001667.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

Genes affected

ARL2 (HGNC:693): (ADP ribosylation factor like GTPase 2) This gene encodes a small GTP-binding protein of the RAS superfamily which functions as an ADP-ribosylation factor (ARF). The encoded protein is one of a functionally distinct group of ARF-like genes. [provided by RefSeq, Jul 2008]

ARL2-SNX15 (HGNC:49197): (ARL2-SNX15 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ADP-ribosylation factor-like 2 (ARL2) and sorting nexin 15 (SNX15) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26371628).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL2	NM_001667.4	c.442C>G	p.Arg148Gly	missense_variant	Exon 5 of 5	ENST00000246747.9	NP_001658.2
ARL2	NM_001199745.2	c.361C>G	p.Arg121Gly	missense_variant	Exon 4 of 4		NP_001186674.1
ARL2-SNX15	NR_037650.2	n.387+3009C>G		intron_variant	Intron 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL2	ENST00000246747.9	c.442C>G	p.Arg148Gly	missense_variant	Exon 5 of 5	1	NM_001667.4	ENSP00000246747.4
ARL2-SNX15	ENST00000301886.3	n.339+3009C>G		intron_variant	Intron 3 of 10	2		ENSP00000476630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000809 AC: 2 AN: 247180 Hom.: 0 AF XY: 0.00000746 AC XY: 1 AN XY: 134024

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1454824 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 723120

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: 0.0000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.033
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.49	N;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;N
REVEL	Uncertain	0.37
Sift	Benign	0.060	T;T;D
Sift4G	Uncertain	0.055	T;T;D
Polyphen		0.0	B;B;.
Vest4		0.24
MVP		0.83
MPC		0.35
ClinPred		0.80	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.43

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: rs375384323; hg19: chr11-64789214;