chr10-100746273-T-C

Variant names:

• chr10-100746273-T-C
• NM_000278.5:c.13T>C

Variant summary

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

The NM_000278.5(PAX2):​c.13T>C​(p.Cys5Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAX2 NM_000278.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.37

Genes affected

PAX2 (HGNC:8616): (paired box 2) PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional supression by the tumor suppressor gene WT1. Mutations within PAX2 have been shown to result in optic nerve colobomas and renal hypoplasia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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
PAX2	NM_000278.5	c.13T>C	p.Cys5Arg	missense_variant	Exon 1 of 10	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.13T>C	p.Cys5Arg	missense_variant	Exon 1 of 10	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461016 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.73	.;.;D;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.0	L;L;L;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Pathogenic	0.65
Sift	Benign	0.38	T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		1.0	D;D;D;.;.
Vest4		0.75
MutPred		0.43		Loss of catalytic residue at M3 (P = 0.0015);Loss of catalytic residue at M3 (P = 0.0015);Loss of catalytic residue at M3 (P = 0.0015);Loss of catalytic residue at M3 (P = 0.0015);Loss of catalytic residue at M3 (P = 0.0015);
MVP		0.98
MPC		2.2
ClinPred		0.76	D
GERP RS		4.8
Varity_R		0.71
gMVP		0.97

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: chr10-102506030;