rs758024780

Variant names:

• chr14-74856974-G-A
• NM_001243007.2:c.1435C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-74856974-G-A
• chr14-74856974-G-T

Variant summary

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

The NM_001243007.2(PROX2):​c.1435C>T​(p.Gln479*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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: PROX2 NM_001243007.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

Genes affected

PROX2 (HGNC:26715): (prospero homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

YLPM1 (HGNC:17798): (YLP motif containing 1) Enables RNA binding activity. Predicted to be involved in regulation of telomere maintenance. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

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
PROX2	NM_001243007.2	c.1435C>T	p.Gln479*	stop_gained	Exon 5 of 6	ENST00000556489.4	NP_001229936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX2	ENST00000556489.4	c.1435C>T	p.Gln479*	stop_gained	Exon 5 of 6	1	NM_001243007.2	ENSP00000451223.2
PROX2	ENST00000673765.1	c.754C>T	p.Gln252*	stop_gained	Exon 4 of 5			ENSP00000501015.1
YLPM1	ENST00000554107.2	c.*1632G>A		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000476212.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461658 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727118

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	46
DANN	Uncertain	1.0
Eigen	Pathogenic	1.3
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.97	D
Vest4		0.45
GERP RS		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr14-75323677;