3-186784669-CAG-C

Variant names:

• chr3-186784669-CAG-C
• NM_001967.4:c.186_187delAG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001967.4(EIF4A2):​c.186_187delAG​(p.Arg62SerfsTer7) variant causes a frameshift 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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF4A2 NM_001967.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.84

Genes affected

EIF4A2 (HGNC:3284): (eukaryotic translation initiation factor 4A2) Enables ATP hydrolysis activity. Involved in negative regulation of RNA-directed 5'-3' RNA polymerase activity. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SNORD2 (HGNC:32678): (small nucleolar RNA, C/D box 2)

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-186784669-CAG-C is Pathogenic according to our data. Variant chr3-186784669-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1722504.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-186784669-CAG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4A2	NM_001967.4	c.186_187delAG	p.Arg62SerfsTer7	frameshift_variant	Exon 3 of 11	ENST00000323963.10	NP_001958.2
SNORD2	NR_002587.1	n.-126_-125delAG		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4A2	ENST00000323963.10	c.186_187delAG	p.Arg62SerfsTer7	frameshift_variant	Exon 3 of 11	1	NM_001967.4	ENSP00000326381.5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures Pathogenic:1

Jun 10, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-186502458;