Variant rs147757229 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014467.3(SRPX2):c.920A>G(p.Gln307Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,209,246 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )

Consequence

SRPX2
NM_014467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.85

Variant links:

Genes affected

SRPX2 (HGNC:30668): (sushi repeat containing protein X-linked 2) This gene encodes a secreted protein that contains three sushi repeat motifs. The encoded protein may play a role in the development of speech and language centers in the brain. This protein may also be involved in angiogenesis. Mutations in this gene are the cause of bilateral perisylvian polymicrogyria, rolandic epilepsy, speech dyspraxia and cognitive disability. [provided by RefSeq, May 2010]

SRPX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3 linkuse as main transcript	c.920A>G	p.Gln307Arg	missense_variant	8/11	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5 linkuse as main transcript	c.920A>G	p.Gln307Arg	missense_variant	8/11	1	NM_014467.3	ENSP00000362095	P1

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

112407

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34573

show subpopulations

Gnomad AFR

AF:

0.000550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000501

AC:

AN:

179783

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

65059

show subpopulations

Gnomad AFR exome

AF:

0.000626

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1096786

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

362382

show subpopulations

Gnomad4 AFR exome

AF:

0.000455

Gnomad4 AMR exome

AF:

0.0000854

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.000169

AC:

AN:

112460

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

34636

show subpopulations

Gnomad4 AFR

AF:

0.000581

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000231

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 27, 2014

- -

Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 20, 2021

This sequence change replaces glutamine with arginine at codon 307 of the SRPX2 protein (p.Gln307Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs147757229, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with SRPX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 198858). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.00030

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.41

Sift

Uncertain

0.019

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.74

MVP

0.69

MPC

0.51

ClinPred

0.20

GERP RS

5.3

Varity_R

0.72

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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