Variant rs2022475 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014467.3(SRPX2):c.356-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 28043 hom., 27378 hem., cov: 23)

Exomes 𝑓: 0.95 ( 330570 hom. 327549 hem. )

Failed GnomAD Quality Control

Consequence

SRPX2
NM_014467.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.07

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:

SRPX2 (HGNC:):

SRPX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-100664736-G-A is Benign according to our data. Variant chrX-100664736-G-A is described in ClinVar as [Benign]. Clinvar id is 670790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3 linkuse as main transcript	c.356-38G>A		intron_variant		ENST00000373004.5	NP_055282.1	O60687

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5 linkuse as main transcript	c.356-38G>A		intron_variant		1	NM_014467.3	ENSP00000362095.3		O60687

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

90935

AN:

110961

Hom.:

28058

Cov.:

AF XY:

0.825

AC XY:

27355

AN XY:

33173

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.913

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.990

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.977

Gnomad OTH

AF:

0.864

GnomAD3 exomes

AF:

0.907

AC:

124705

AN:

137432

Hom.:

40271

AF XY:

0.913

AC XY:

37984

AN XY:

41594

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.933

Gnomad ASJ exome

AF:

0.972

Gnomad EAS exome

AF:

0.838

Gnomad SAS exome

AF:

0.842

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.978

Gnomad OTH exome

AF:

0.944

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.952

AC:

1015110

AN:

1066367

Hom.:

330570

Cov.:

AF XY:

0.951

AC XY:

327549

AN XY:

344355

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.929

Gnomad4 ASJ exome

AF:

0.971

Gnomad4 EAS exome

AF:

0.848

Gnomad4 SAS exome

AF:

0.849

Gnomad4 FIN exome

AF:

0.988

Gnomad4 NFE exome

AF:

0.978

Gnomad4 OTH exome

AF:

0.922

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.819

AC:

90935

AN:

111013

Hom.:

28043

Cov.:

AF XY:

0.824

AC XY:

27378

AN XY:

33235

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.913

Gnomad4 ASJ

AF:

0.975

Gnomad4 EAS

AF:

0.845

Gnomad4 SAS

AF:

0.833

Gnomad4 FIN

AF:

0.990

Gnomad4 NFE

AF:

0.977

Gnomad4 OTH

AF:

0.862

Alfa

AF:

0.939

Hom.:

56776

Bravo

AF:

0.801

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.1

DANN

Benign

0.49

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