1-155981711-A-G

Variant names:

• chr1-155981711-A-G
• rs1889532
• ENST00000610146.1:n.882A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000610146.1(ARHGEF2-AS2):​n.882A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,020 control chromosomes in the GnomAD database, including 7,050 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 0.28 (7042 hom., cov: 31)
  • Exomes 𝑓: 0.34 (8 hom.)
• Consequence: ARHGEF2-AS2 ENST00000610146.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 22 publications found

Genes affected

ARHGEF2-AS2 (HGNC:55175): (ARHGEF2 antisense RNA 2)

ARHGEF2 (HGNC:682): (Rho/Rac guanine nucleotide exchange factor 2) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

ARHGEF2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with midbrain and hindbrain malformations

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000610146.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF2-AS2	NR_183459.1		n.901A>G		non_coding_transcript_exon	Exon 2 of 2
	ARHGEF2-AS2	NR_183460.1		n.1037A>G		non_coding_transcript_exon	Exon 3 of 3
	ARHGEF2-AS2	NR_183461.1		n.1038A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF2-AS2	ENST00000610146.1	TSL:4	n.882A>G		non_coding_transcript_exon	Exon 2 of 2
	ARHGEF2-AS2	ENST00000756615.1		n.259A>G		non_coding_transcript_exon	Exon 3 of 4
	ARHGEF2-AS2	ENST00000756616.1		n.404A>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43135 AN: 151814 Hom.: 7036 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.341 AC: 30 AN: 88 Hom.: 8 Cov.: 0 AF XY: 0.359 AC XY: 23 AN XY: 64

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.324 AC: 22 AN: 68

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.284 AC: 43152 AN: 151932 Hom.: 7042 Cov.: 31 AF XY: 0.289 AC XY: 21483 AN XY: 74238

African (AFR) AF: 0.258 AC: 10682 AN: 41410

American (AMR) AF: 0.324 AC: 4951 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4257 AN: 5168

South Asian (SAS) AF: 0.336 AC: 1614 AN: 4804

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10562

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17328 AN: 67946

Other (OTH) AF: 0.285 AC: 600 AN: 2108

Alfa AF: 0.259 Hom.: 9004

Bravo AF: 0.293

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1889532; hg19: chr1-155951502;