rs12648800

chr4-5637692-G-Achr4-5637692-G-T

Variant summary

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

The NM_147127.5(EVC2):c.1470+2822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,070 control chromosomes in the GnomAD database, including 4,502 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 0.22 (4502 hom., cov: 32)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC2	NM_147127.5	c.1470+2822C>T		intron_variant		ENST00000344408.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC2	ENST00000344408.10	c.1470+2822C>T		intron_variant		1	NM_147127.5	P2
EVC2	ENST00000310917.6	c.1230+2822C>T		intron_variant		1		A2
EVC2	ENST00000475313.5	c.1230+2822C>T		intron_variant, NMD_transcript_variant		1
EVC2	ENST00000509670.1	c.1222+2830C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32942 AN: 151952 Hom.: 4495 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.217 AC: 32957 AN: 152070 Hom.: 4502 Cov.: 32 AF XY: 0.225 AC XY: 16704 AN XY: 74328

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.217

Alfa AF: 0.107 Hom.: 169

Bravo AF: 0.221

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.73
Dann	Benign	0.40

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: rs12648800; hg19: chr4-5639419;