19-10223987-T-G

Position:

chr19-10223987-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004230.4(S1PR2):c.919A>C(p.Arg307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,608,656 control chromosomes in the GnomAD database, including 278,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28491 hom., cov: 33)

Exomes 𝑓: 0.58 ( 249795 hom. )

Consequence

S1PR2
NM_004230.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0480

Variant links:

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]

S1PR2 links:

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]

DNMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-10223987-T-G is Benign according to our data. Variant chr19-10223987-T-G is described in ClinVar as [Benign]. Clinvar id is 506085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S1PR2	NM_004230.4 linkuse as main transcript	c.919A>C	p.Arg307=	synonymous_variant	2/2	ENST00000646641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
S1PR2	ENST00000646641.1 linkuse as main transcript	c.919A>C	p.Arg307=	synonymous_variant	2/2		NM_004230.4	P1
DNMT1	ENST00000588952.5 linkuse as main transcript	c.-401-5118A>C		intron_variant		5
DNMT1	ENST00000592342.5 linkuse as main transcript	c.-284+7217A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91661

AN:

151956

Hom.:

28471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.537

AC:

128942

AN:

239966

Hom.:

36064

AF XY:

0.542

AC XY:

71166

AN XY:

131394

show subpopulations

Gnomad AFR exome

AF:

0.733

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.515

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.581

AC:

845901

AN:

1456582

Hom.:

249795

Cov.:

AF XY:

0.579

AC XY:

419520

AN XY:

724116

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.603

AC:

91727

AN:

152074

Hom.:

28491

Cov.:

AF XY:

0.594

AC XY:

44172

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.735

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.497

Hom.:

2502

Bravo

AF:

0.612

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Arg307Arg in exon 2 of S1PR2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 73.32% (6474/8830) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs2116942). -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal recessive nonsyndromic hearing loss 68

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.4

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over