chr11-65020496-C-G

Variant names:

• chr11-65020496-C-G
• rs762451444
• NM_001667.4:c.417C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001667.4(ARL2):​c.417C>G​(p.Arg139Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,476 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. Synonymous variant affecting the same amino acid position (i.e. R139R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARL2 NM_001667.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.40
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-4.4 with no splicing effect.

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.417C>G	p.Arg139Arg	synonymous	Exon 4 of 5	NP_001658.2	P36404-1
	ARL2	NM_001199745.2		c.340-1225C>G		intron	N/A	NP_001186674.1	P36404-2
	ARL2-SNX15	NR_037650.2		n.387+1763C>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.417C>G	p.Arg139Arg	synonymous	Exon 4 of 5	ENSP00000246747.4	P36404-1
	ARL2-SNX15	ENST00000301886.3	TSL:2	n.339+1763C>G		intron	N/A	ENSP00000476630.1	V9GYD0
	ARL2	ENST00000529384.5	TSL:3	c.417C>G	p.Arg139Arg	synonymous	Exon 4 of 6	ENSP00000436021.1	P36404-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456476 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724120

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109176

Other (OTH) AF: 0.00 AC: 0 AN: 60150

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.48
DANN	Benign	0.77
PhyloP100		-4.4

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: rs762451444; hg19: chr11-64787968;