chr1-155948089-T-A

Position:

• chr1-155948089-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001162383.2(ARHGEF2):​c.2888-74A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 1,195,820 control chromosomes in the GnomAD database, including 486,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (51648 hom., cov: 31)
  • Exomes 𝑓: 0.91 (434895 hom.)
• Consequence: ARHGEF2 NM_001162383.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.372

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-155948089-T-A is Benign according to our data. Variant chr1-155948089-T-A is described in ClinVar as [Benign]. Clinvar id is 1192410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF2	NM_001162383.2	c.2888-74A>T		intron_variant		ENST00000361247.9	NP_001155855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF2	ENST00000361247.9	c.2888-74A>T		intron_variant		1	NM_001162383.2	ENSP00000354837	P4

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122296 AN: 151940 Hom.: 51637 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.910 AC: 949745 AN: 1043762 Hom.: 434895 AF XY: 0.909 AC XY: 473671 AN XY: 521186

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.946

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.804 AC: 122321 AN: 152058 Hom.: 51648 Cov.: 31 AF XY: 0.806 AC XY: 59932 AN XY: 74336

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.840

Alfa AF: 0.859 Hom.: 6799

Bravo AF: 0.794

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurodevelopmental disorder with midbrain and hindbrain malformations Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.69

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: rs1010033; hg19: chr1-155917880;