chr17-8313028-GGTCCCCCGTCGGGCC-G

Position:

• chr17-8313028-GGTCCCCCGTCGGGCC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_173728.4(ARHGEF15):​c.709_723del​(p.Val237_Ala241del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ARHGEF15 NM_173728.4 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.00

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_173728.4.
• PP5: Variant 17-8313028-GGTCCCCCGTCGGGCC-G is Pathogenic according to our data. Variant chr17-8313028-GGTCCCCCGTCGGGCC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 495290.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.709_723del	p.Val237_Ala241del	inframe_deletion	3/16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.709_723del	p.Val237_Ala241del	inframe_deletion	3/16	1	NM_173728.4	ENSP00000355026	P1
ARHGEF15	ENST00000421050.2	c.709_723del	p.Val237_Ala241del	inframe_deletion	3/16	1		ENSP00000412505	P1
ARHGEF15	ENST00000455564.3	n.1103_1117del		non_coding_transcript_exon_variant	2/2	2
ARHGEF15	ENST00000581809.1			coding_sequence_variant, 5_prime_UTR_variant, NMD_transcript_variant	1/3	3		ENSP00000463875

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

NeuroMeGen, Hospital Clinico Santiago de Compostela

Jan 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555546796; hg19: chr17-8216346;