rs863225051

chr12-123624798-TTCC-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_001414.4(EIF2B1):c.613_615del(p.Gly205del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G205G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EIF2B1 NM_001414.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.71

Genes affected

EIF2B1 (HGNC:3257): (eukaryotic translation initiation factor 2B subunit alpha) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001414.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 12-123624798-TTCC-T is Pathogenic according to our data. Variant chr12-123624798-TTCC-T is described in ClinVar as [Pathogenic]. Clinvar id is 217280.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2B1	NM_001414.4	c.613_615del	p.Gly205del	inframe_deletion	7/9	ENST00000424014.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B1	ENST00000424014.7	c.613_615del	p.Gly205del	inframe_deletion	7/9	1	NM_001414.4	P1
EIF2B1	ENST00000534960.5	c.*20_*22del		3_prime_UTR_variant	5/6	5
EIF2B1	ENST00000539951.5	c.512+1624_512+1626del		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Vanishing white matter disease Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 19, 2015

- -

Computational scores

Source: dbNSFP v4.3

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: rs863225051; hg19: chr12-124109345;