X-66599718-G-T

Variant names:

• chrX-66599718-G-T
• NM_021783.5:c.660C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021783.5(EDA2R):​c.660C>A​(p.Asp220Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,393 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: EDA2R NM_021783.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

EDA2R (HGNC:17756): (ectodysplasin A2 receptor) The protein encoded by this gene is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains cysteine-rich repeats and a single transmembrane domain. This protein binds to the EDA-A2 isoform of ectodysplasin, which plays an important role in maintenance of hair and teeth. Alternatively spliced transcript variants encodes distinct protein isoforms. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08250308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA2R	NM_021783.5	c.660C>A	p.Asp220Glu	missense_variant	Exon 6 of 7	ENST00000374719.8	NP_068555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA2R	ENST00000374719.8	c.660C>A	p.Asp220Glu	missense_variant	Exon 6 of 7	1	NM_021783.5	ENSP00000363851.3
EDA2R	ENST00000253392.5	c.723C>A	p.Asp241Glu	missense_variant	Exon 6 of 6	1		ENSP00000253392.5
EDA2R	ENST00000396050.5	c.723C>A	p.Asp241Glu	missense_variant	Exon 6 of 7	5		ENSP00000379365.2
EDA2R	ENST00000451436.6	c.660C>A	p.Asp220Glu	missense_variant	Exon 6 of 7	5		ENSP00000415242.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096393 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 361987

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.024
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T;.
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.72	.;T;T;.
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.080	N;.;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.20	T;.;.;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.43	B;P;B;P
Vest4		0.26
MutPred		0.10		Gain of glycosylation at T225 (P = 0.136);.;Gain of glycosylation at T225 (P = 0.136);.;
MVP		0.48
ClinPred		0.64	D
GERP RS		-5.0
Varity_R		0.062
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-65819560;