14-74855624-A-G

Variant summary

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

The NM_001243007.2(PROX2):c.1609-322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 213,920 control chromosomes in the GnomAD database, including 34,559 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 0.58 (25948 hom., cov: 34)
  • Exomes 𝑓: 0.52 (8611 hom.)
• Consequence: PROX2 NM_001243007.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX2	NM_001243007.2	c.1609-322T>C		intron_variant		ENST00000556489.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX2	ENST00000556489.4	c.1609-322T>C		intron_variant		1	NM_001243007.2	P1
YLPM1	ENST00000554107.2	c.*282A>G		3_prime_UTR_variant	4/4	3
PROX2	ENST00000673765.1	c.928-322T>C		intron_variant
YLPM1	ENST00000553381.1	n.645A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87498 AN: 152052 Hom.: 25911 Cov.: 34

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.524 AC: 32368 AN: 61750 Hom.: 8611 Cov.: 0 AF XY: 0.524 AC XY: 16358 AN XY: 31216

Gnomad4 AFR exome AF: 0.719

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.576 AC: 87585 AN: 152170 Hom.: 25948 Cov.: 34 AF XY: 0.578 AC XY: 42989 AN XY: 74394

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.554

Alfa AF: 0.494 Hom.: 7280

Bravo AF: 0.567

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.2
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs10483863; hg19: chr14-75322327;