Genetic Variant SRPX2:c.163+291T>G (chrX-100651156-T-G) – 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.163+291T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 326,104 control chromosomes in the GnomAD database, including 414 homozygotes. There are 3,924 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 202 hom., 1671 hem., cov: 22)

Exomes 𝑓: 0.033 ( 212 hom. 2253 hem. )

Consequence

SRPX2
NM_014467.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.551

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=-0.59).

BP6

Variant X-100651156-T-G is Benign according to our data. Variant chrX-100651156-T-G is described in ClinVar as [Benign]. Clinvar id is 1247373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3 link	c.163+291T>G		intron_variant	Intron 3 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.163+291T>G		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3		O60687

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

5379

AN:

111235

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0148

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.0210

Gnomad NFE

AF:

0.00737

Gnomad OTH

AF:

0.0340

GnomAD4 exome

AF:

0.0327

AC:

7033

AN:

214814

Hom.:

212

AF XY:

0.0435

AC XY:

2253

AN XY:

51794

show subpopulations

African (AFR)

AF:

0.116

AC:

860

AN:

7405

American (AMR)

AF:

0.0414

AC:

398

AN:

9616

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

AN:

6630

East Asian (EAS)

AF:

0.121

AC:

1800

AN:

14931

South Asian (SAS)

AF:

0.120

AC:

1822

AN:

15233

European-Finnish (FIN)

AF:

0.0548

AC:

711

AN:

12983

Middle Eastern (MID)

AF:

0.0297

AC:

AN:

874

European-Non Finnish (NFE)

AF:

0.00683

AC:

913

AN:

133728

Other (OTH)

AF:

0.0303

AC:

406

AN:

13414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

199

398

596

795

994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0485

AC:

5394

AN:

111290

Hom.:

202

Cov.:

AF XY:

0.0499

AC XY:

1671

AN XY:

33520

show subpopulations

African (AFR)

AF:

0.114

AC:

3469

AN:

30563

American (AMR)

AF:

0.0375

AC:

393

AN:

10475

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

AN:

2636

East Asian (EAS)

AF:

0.111

AC:

388

AN:

3497

South Asian (SAS)

AF:

0.112

AC:

294

AN:

2618

European-Finnish (FIN)

AF:

0.0598

AC:

360

AN:

6025

Middle Eastern (MID)

AF:

0.0184

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00737

AC:

391

AN:

53053

Other (OTH)

AF:

0.0368

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0315

Hom.:

151

Bravo

AF:

0.0517

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

- -

Jul 15, 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

-0.59

CADD

Benign

3.3

(source)

DANN

Benign

0.90

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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-100651156-T-G

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