11-65021742-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R148C) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001667.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL2	NM_001667.4	MANE Select	c.442C>G	p.Arg148Gly	missense	Exon 5 of 5	NP_001658.2	P36404-1
	ARL2	NM_001199745.2		c.361C>G	p.Arg121Gly	missense	Exon 4 of 4	NP_001186674.1	P36404-2
	ARL2-SNX15	NR_037650.2		n.387+3009C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL2	ENST00000246747.9	TSL:1 MANE Select	c.442C>G	p.Arg148Gly	missense	Exon 5 of 5	ENSP00000246747.4	P36404-1
	ARL2-SNX15	ENST00000301886.3	TSL:2	n.339+3009C>G		intron	N/A	ENSP00000476630.1	V9GYD0
	ARL2	ENST00000529384.5	TSL:3	c.442C>G	p.Arg148Gly	missense	Exon 5 of 6	ENSP00000436021.1	P36404-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000809 AC: 2 AN: 247180 AF XY: 0.00000746

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1109044

Other (OTH) AF: 0.00 AC: 0 AN: 60066

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.033
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.49	N
PhyloP100		3.8
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.37
Sift	Benign	0.060	T
Sift4G	Uncertain	0.055	T
Polyphen		0.0	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
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs375384323; hg19: chr11-64789214;