chr2-108894829-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_022336.4(EDAR):c.*2078T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 152,350 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EDAR
NM_022336.4 3_prime_UTR
NM_022336.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.370
Genes affected
EDAR (HGNC:2895): (ectodysplasin A receptor) This gene encodes a member of the tumor necrosis factor receptor family. The encoded transmembrane protein is a receptor for the soluble ligand ectodysplasin A, and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 2-108894829-A-G is Benign according to our data. Variant chr2-108894829-A-G is described in ClinVar as [Benign]. Clinvar id is 894456.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00312 (476/152350) while in subpopulation AFR AF= 0.0105 (437/41586). AF 95% confidence interval is 0.0097. There are 3 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDAR | NM_022336.4 | c.*2078T>C | 3_prime_UTR_variant | 12/12 | ENST00000258443.7 | ||
EDAR | XM_006712204.2 | c.*2078T>C | 3_prime_UTR_variant | 11/11 | |||
RANBP2 | XM_047445367.1 | c.8370+121783A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDAR | ENST00000258443.7 | c.*2078T>C | 3_prime_UTR_variant | 12/12 | 1 | NM_022336.4 | P1 | ||
EDAR | ENST00000376651.1 | c.*2078T>C | 3_prime_UTR_variant | 11/11 | 2 | ||||
EDAR | ENST00000409271.5 | c.*2078T>C | 3_prime_UTR_variant | 12/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00314 AC: 478AN: 152232Hom.: 3 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 6Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 4
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypohidrotic ectodermal dysplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at