chrX-66604439-G-C

Variant names:

• chrX-66604439-G-C
• rs12837393
• NM_021783.5:c.334C>G

Variant summary

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

The NM_021783.5(EDA2R):​c.334C>G​(p.Pro112Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: EDA2R NM_021783.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA2R	NM_021783.5	c.334C>G	p.Pro112Ala	missense_variant	Exon 4 of 7	ENST00000374719.8	NP_068555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA2R	ENST00000374719.8	c.334C>G	p.Pro112Ala	missense_variant	Exon 4 of 7	1	NM_021783.5	ENSP00000363851.3
EDA2R	ENST00000253392.5	c.334C>G	p.Pro112Ala	missense_variant	Exon 3 of 6	1		ENSP00000253392.5
EDA2R	ENST00000396050.5	c.334C>G	p.Pro112Ala	missense_variant	Exon 3 of 7	5		ENSP00000379365.2
EDA2R	ENST00000451436.6	c.334C>G	p.Pro112Ala	missense_variant	Exon 4 of 7	5		ENSP00000415242.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000553 AC: 1 AN: 180972 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65624

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;.;D;.
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.86	.;D;D;.
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.1	D;D;.;D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.92	P;D;P;D
Vest4		0.43
MutPred		0.69		Loss of glycosylation at P112 (P = 0.0255);Loss of glycosylation at P112 (P = 0.0255);Loss of glycosylation at P112 (P = 0.0255);Loss of glycosylation at P112 (P = 0.0255);
MVP		0.19
ClinPred		0.73	D
GERP RS		3.4
Varity_R		0.37
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs12837393; hg19: chrX-65824281;