rs8014204

Variant names:

• chr14-74856091-G-A
• rs8014204
• NM_001243007.2:c.1608+710C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243007.2(PROX2):​c.1608+710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,202 control chromosomes in the GnomAD database, including 33,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33770 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PROX2 NM_001243007.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX2	NM_001243007.2	c.1608+710C>T		intron_variant	Intron 5 of 5	ENST00000556489.4	NP_001229936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX2	ENST00000556489.4	c.1608+710C>T		intron_variant	Intron 5 of 5	1	NM_001243007.2	ENSP00000451223.2
YLPM1	ENST00000554107.2	c.*749G>A		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000476212.1
PROX2	ENST00000673765.1	c.927+710C>T		intron_variant	Intron 4 of 4			ENSP00000501015.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98244 AN: 152072 Hom.: 33725 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.500 AC: 5 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.646 AC: 98343 AN: 152192 Hom.: 33770 Cov.: 33 AF XY: 0.649 AC XY: 48287 AN XY: 74394

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.619

Alfa AF: 0.543 Hom.: 34946

Bravo AF: 0.644

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.51

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: rs8014204; hg19: chr14-75322794;