chrX-66599554-C-G

Variant names:

• chrX-66599554-C-G
• NM_021783.5:c.824G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021783.5(EDA2R):​c.824G>C​(p.Gly275Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,076,628 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000019 (0 hom. 1 hem.)
• Consequence: EDA2R NM_021783.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04383591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA2R	NM_021783.5	c.824G>C	p.Gly275Ala	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.824G>C	p.Gly275Ala	missense_variant	Exon 6 of 7	1	NM_021783.5	ENSP00000363851.3
EDA2R	ENST00000253392.5	c.887G>C	p.Gly296Ala	missense_variant	Exon 6 of 6	1		ENSP00000253392.5
EDA2R	ENST00000396050.5	c.887G>C	p.Gly296Ala	missense_variant	Exon 6 of 7	5		ENSP00000379365.2
EDA2R	ENST00000451436.6	c.824G>C	p.Gly275Ala	missense_variant	Exon 6 of 7	5		ENSP00000415242.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1076628 Hom.: 0 Cov.: 32 AF XY: 0.00000286 AC XY: 1 AN XY: 349578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000344

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.051
DANN	Benign	0.075
DEOGEN2	Benign	0.072	T;.;T;.
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.60	.;T;T;.
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;.;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.19	N;.;.;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;.;.;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.010	B;B;B;B
Vest4		0.045
MutPred		0.15		Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);.;
MVP		0.60
ClinPred		0.063	T
GERP RS		0.83
Varity_R		0.044
gMVP		0.15

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-65819396;