19-10222312-C-T

Position:

• chr19-10222312-C-T

Variant summary

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

The NM_004230.4(S1PR2):​c.*1532G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,832 control chromosomes in the GnomAD database, including 19,261 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 0.49 (19249 hom., cov: 30)
  • Exomes 𝑓: 0.55 (12 hom.)
• Consequence: S1PR2 NM_004230.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

Genes affected

S1PR2 (HGNC:3169): (sphingosine-1-phosphate receptor 2) This gene encodes a member of the G protein-coupled receptors, as well as the EDG family of proteins. The encoded protein is a receptor for sphingosine 1-phosphate, which participates in cell proliferation, survival, and transcriptional activation. Defects in this gene have been associated with congenital profound deafness. [provided by RefSeq, Mar 2016]

DNMT1 (HGNC:2976): (DNA methyltransferase 1) This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S1PR2	NM_004230.4	c.*1532G>A		3_prime_UTR_variant	2/2	ENST00000646641.1	NP_004221.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR2	ENST00000646641.1	c.*1532G>A		3_prime_UTR_variant	2/2		NM_004230.4	ENSP00000496438.1
DNMT1	ENST00000588952.5	c.-401-3443G>A		intron_variant		5		ENSP00000467050.1
DNMT1	ENST00000592342.5	c.-284+8892G>A		intron_variant		3		ENSP00000465993.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74858 AN: 151636 Hom.: 19255 Cov.: 30

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.551 AC: 43 AN: 78 Hom.: 12 Cov.: 0 AF XY: 0.550 AC XY: 22 AN XY: 40

Gnomad4 EAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.714

GnomAD4 genome AF: 0.493 AC: 74872 AN: 151754 Hom.: 19249 Cov.: 30 AF XY: 0.486 AC XY: 36010 AN XY: 74148

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.546

Alfa AF: 0.571 Hom.: 34766

Bravo AF: 0.493

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.66

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: rs10409243; hg19: chr19-10332988;