2-31386525-G-C

Position:

• chr2-31386525-G-C

Variant summary

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

The ENST00000379416.4(XDH):​c.682C>G​(p.Arg228Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
• Consequence: XDH ENST00000379416.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

Genes affected

XDH (HGNC:12805): (xanthine dehydrogenase) Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism. [provided by RefSeq, Jan 2014]

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=0.22522166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.682C>G	p.Arg228Gly	missense_variant	9/36	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.682C>G	p.Arg228Gly	missense_variant	9/36		XP_011531397.1
XDH	XM_011533096.3	c.682C>G	p.Arg228Gly	missense_variant	9/29		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.682C>G	p.Arg228Gly	missense_variant	9/36	1	NM_000379.4	ENSP00000368727	P1
XDH	ENST00000491727.5	n.225C>G		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135884

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.5
DANN	Benign	0.82
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.33	T
Sift4G	Benign	0.38	T
Polyphen		0.022	B
Vest4		0.57
MutPred		0.41		Loss of MoRF binding (P = 0.0072);
MVP		0.25
MPC		0.048
ClinPred		0.082	T
GERP RS		-2.9
Varity_R		0.18
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs119460972; hg19: chr2-31609391; COSMIC: COSV65151007; COSMIC: COSV65151007;