rs8014204

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556489.4(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 ENST00000556489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX2	NM_001243007.2	MANE Select	c.1608+710C>T		intron	N/A	NP_001229936.1
	PROX2	NM_001384314.1		c.1608+710C>T		intron	N/A	NP_001371243.1
	PROX2	NM_001080408.3		c.927+710C>T		intron	N/A	NP_001073877.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX2	ENST00000556489.4	TSL:1 MANE Select	c.1608+710C>T		intron	N/A	ENSP00000451223.2
	YLPM1	ENST00000554107.2	TSL:3	c.*749G>A		3_prime_UTR	Exon 4 of 4	ENSP00000476212.1
	PROX2	ENST00000673765.1		c.927+710C>T		intron	N/A	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 5 AN: 10

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.903 AC: 37526 AN: 41542

American (AMR) AF: 0.540 AC: 8248 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2331 AN: 5170

South Asian (SAS) AF: 0.673 AC: 3246 AN: 4826

European-Finnish (FIN) AF: 0.663 AC: 7021 AN: 10596

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36073 AN: 67998

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.561 Hom.: 81904

Bravo AF: 0.644

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.51
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8014204; hg19: chr14-75322794;