rs1385698

Positions:

• chrX-66602765-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021783.5(EDA2R):​c.385A>G​(p.Thr129Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.94 (34351 hom., 29940 hem., cov: 22)
  • Exomes 𝑓: 0.99 (360513 hom. 352687 hem.)
  • Failed GnomAD Quality Control
• Consequence: EDA2R NM_021783.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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]

EDA2R (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1831476E-6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5	c.385A>G	p.Thr129Ala	missense_variant	5/7	ENST00000374719.8	NP_068555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA2R	ENST00000374719.8	c.385A>G	p.Thr129Ala	missense_variant	5/7	1	NM_021783.5	ENSP00000363851.3
EDA2R	ENST00000253392.5	c.385A>G	p.Thr129Ala	missense_variant	4/6	1		ENSP00000253392.5
EDA2R	ENST00000396050.5	c.385A>G	p.Thr129Ala	missense_variant	4/7	5		ENSP00000379365.2
EDA2R	ENST00000451436.6	c.385A>G	p.Thr129Ala	missense_variant	5/7	5		ENSP00000415242.3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 102510 AN: 109538 Hom.: 34354 Cov.: 22 AF XY: 0.941 AC XY: 29886 AN XY: 31776

Gnomad AFR AF: 0.776

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.996

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.955

GnomAD3 exomes AF: 0.981 AC: 149078 AN: 151976 Hom.: 52177 AF XY: 0.989 AC XY: 42796 AN XY: 43292

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.989

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.992

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.993 AC: 1078064 AN: 1085336 Hom.: 360513 Cov.: 39 AF XY: 0.995 AC XY: 352687 AN XY: 354566

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.988

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.936 AC: 102558 AN: 109596 Hom.: 34351 Cov.: 22 AF XY: 0.940 AC XY: 29940 AN XY: 31844

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.955

Alfa AF: 0.990 Hom.: 77622

Bravo AF: 0.926

TwinsUK AF: 0.999 AC: 3706

ALSPAC AF: 1.00 AC: 2888

ESP6500AA AF: 0.778 AC: 2985

ESP6500EA AF: 1.00 AC: 6723

ExAC AF: 0.978 AC: 115776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.7
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T;.;T;.
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.039	.;T;T;.
MetaRNN	Benign	0.0000012	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.070	N;N;.;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.016
ClinPred		0.0063	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1385698; hg19: chrX-65822607; COSMIC: COSV53630236;