rs6446384

Positions:

• chr4-5642651-T-A
• chr4-5642651-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147127.5(EVC2):​c.1146-1813A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,052 control chromosomes in the GnomAD database, including 36,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36365 hom., cov: 32)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC2	NM_147127.5	c.1146-1813A>T		intron_variant		ENST00000344408.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC2	ENST00000344408.10	c.1146-1813A>T		intron_variant		1	NM_147127.5	P2
EVC2	ENST00000310917.6	c.906-1813A>T		intron_variant		1		A2
EVC2	ENST00000475313.5	c.906-1813A>T		intron_variant, NMD_transcript_variant		1
EVC2	ENST00000509670.1	c.906-1813A>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104149 AN: 151934 Hom.: 36326 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.686 AC: 104237 AN: 152052 Hom.: 36365 Cov.: 32 AF XY: 0.682 AC XY: 50695 AN XY: 74314

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.676

Alfa AF: 0.679 Hom.: 4408

Bravo AF: 0.694

Asia WGS AF: 0.594 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.084
DANN	Benign	0.31

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: rs6446384; hg19: chr4-5644378;