Variant chrX-66602794-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021783.5(EDA2R):c.356C>T(p.Ala119Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000938 in 1,066,356 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.4e-7 ( 0 hom. 0 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3527051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5 link	c.356C>T	p.Ala119Val	missense_variant	5/7	ENST00000374719.8	NP_068555.2	Q9HAV5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EDA2R	ENST00000374719.8 link	c.356C>T	p.Ala119Val	missense_variant	5/7	1	NM_021783.5	ENSP00000363851.3	Q9HAV5-1
EDA2R	ENST00000253392.5 link	c.356C>T	p.Ala119Val	missense_variant	4/6	1		ENSP00000253392.5	Q9HAV5-2
EDA2R	ENST00000396050.5 link	c.356C>T	p.Ala119Val	missense_variant	4/7	5		ENSP00000379365.2	Q9HAV5-2
EDA2R	ENST00000451436.6 link	c.356C>T	p.Ala119Val	missense_variant	5/7	5		ENSP00000415242.3	Q9HAV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.38e-7

AC:

AN:

1066356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

340162

show subpopulations

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:

0.0000204

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.356C>T (p.A119V) alteration is located in exon 4 (coding exon 4) of the EDA2R gene. This alteration results from a C to T substitution at nucleotide position 356, causing the alanine (A) at amino acid position 119 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;T;.

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

.;T;T;.

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.8

L;L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.21

Sift

Benign

0.29

T;T;.;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.29

B;P;B;P

Vest4

0.13

MutPred

0.29

Loss of disorder (P = 0.0978);Loss of disorder (P = 0.0978);Loss of disorder (P = 0.0978);Loss of disorder (P = 0.0978);

MVP

0.77

ClinPred

0.80

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over