4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_147127.5(EVC2):c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC(p.Lys1293_Lys1300dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVC2 NM_147127.5 inframe_insertion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.03

Genes affected

EVC2 (HGNC:19747): (EvC ciliary complex subunit 2) This gene encodes a protein that functions in bone formation and skeletal development. Mutations in this gene, as well as in a neighboring gene that lies in a head-to-head configuration, cause Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia that is also known as chondroectodermal dysplasia. Mutations in this gene also cause acrofacial dysostosis Weyers type, also referred to as Curry-Hall syndrome, a disease that combines limb and facial abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_147127.5.
• PP5: Variant 4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC is Pathogenic according to our data. Variant chr4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183329.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC2	NM_147127.5	c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC	p.Lys1293_Lys1300dup	inframe_insertion	22/22	ENST00000344408.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC2	ENST00000344408.10	c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC	p.Lys1293_Lys1300dup	inframe_insertion	22/22	1	NM_147127.5	P2
EVC2	ENST00000310917.6	c.3653_3654insGAAAAAGAAGAACTTTTTGAATGC	p.Lys1213_Lys1220dup	inframe_insertion	22/22	1		A2
EVC2	ENST00000475313.5	c.3419+2376_3419+2377insGAAAAAGAAGAACTTTTTGAATGC		intron_variant, NMD_transcript_variant		1
EVC2	ENST00000509670.1	c.*2286_*2287insGAAAAAGAAGAACTTTTTGAATGC		3_prime_UTR_variant, NMD_transcript_variant	23/23	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Meckel-Gruber syndrome Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre

Dec 01, 2014

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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: rs730882232; hg19: chr4-5564608;