Genetic Variant SRPX2:c.83-100T>C (chrX-100650685-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014467.3(SRPX2):c.83-100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 769,784 control chromosomes in the GnomAD database, including 652 homozygotes. There are 8,106 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 200 hom., 1663 hem., cov: 22)

Exomes 𝑓: 0.027 ( 452 hom. 6443 hem. )

Consequence

SRPX2
NM_014467.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.306

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-100650685-T-C is Benign according to our data. Variant chrX-100650685-T-C is described in ClinVar as [Benign]. Clinvar id is 1239134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3 link	c.83-100T>C		intron_variant	Intron 2 of 10	ENST00000373004.5	NP_055282.1	O60687

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5 link	c.83-100T>C		intron_variant	Intron 2 of 10	1	NM_014467.3	ENSP00000362095.3		O60687

Frequencies

GnomAD3 genomes

AF:

0.0490

AC:

5442

AN:

111062

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0148

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0588

Gnomad MID

AF:

0.0208

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.0321

GnomAD4 exome

AF:

0.0271

AC:

17819

AN:

658667

Hom.:

452

AF XY:

0.0345

AC XY:

6443

AN XY:

186561

show subpopulations

African (AFR)

AF:

0.125

AC:

2247

AN:

18005

American (AMR)

AF:

0.0468

AC:

1414

AN:

30188

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

258

AN:

16114

East Asian (EAS)

AF:

0.121

AC:

3262

AN:

27037

South Asian (SAS)

AF:

0.110

AC:

4752

AN:

43171

European-Finnish (FIN)

AF:

0.0559

AC:

2086

AN:

37318

Middle Eastern (MID)

AF:

0.0307

AC:

102

AN:

3320

European-Non Finnish (NFE)

AF:

0.00597

AC:

2700

AN:

452039

Other (OTH)

AF:

0.0317

AC:

998

AN:

31475

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

579

1158

1737

2316

2895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0491

AC:

5455

AN:

111117

Hom.:

200

Cov.:

AF XY:

0.0499

AC XY:

1663

AN XY:

33339

show subpopulations

African (AFR)

AF:

0.115

AC:

3515

AN:

30509

American (AMR)

AF:

0.0375

AC:

393

AN:

10477

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

AN:

2639

East Asian (EAS)

AF:

0.118

AC:

415

AN:

3530

South Asian (SAS)

AF:

0.114

AC:

294

AN:

2568

European-Finnish (FIN)

AF:

0.0588

AC:

349

AN:

5935

Middle Eastern (MID)

AF:

0.0183

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00741

AC:

393

AN:

53043

Other (OTH)

AF:

0.0350

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

168

337

505

674

842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0258

Hom.:

2212

Bravo

AF:

0.0526

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.83

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chrX-100650685-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over