rs121918363

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014467.3(SRPX2):c.980A>G(p.Asn327Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000871 in 1,209,994 control chromosomes in the GnomAD database, including 2 homozygotes. There are 334 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N327K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 12 hem., cov: 24)

Exomes 𝑓: 0.00092 ( 2 hom. 322 hem. )

Consequence

SRPX2
NM_014467.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:6

Conservation

PhyloP100: 1.70

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

rolandic epilepsy-speech dyspraxia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
polymicrogyria, bilateral perisylvian, X-linked
Inheritance: XL Classification: LIMITED Submitted by: G2P
rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked
Inheritance: XL Classification: LIMITED, NO_KNOWN Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
epilepsy
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

SRPX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04739812).

BP6

Variant X-100667292-A-G is Benign according to our data. Variant chrX-100667292-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 10775.

BS2

High AC in GnomAd4 at 45 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	NM_014467.3	MANE Select	c.980A>G	p.Asn327Ser	missense	Exon 9 of 11	NP_055282.1	O60687

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.980A>G	p.Asn327Ser	missense	Exon 9 of 11	ENSP00000362095.3	O60687
SRPX2	ENST00000640282.1	TSL:5	c.26A>G	p.Asn9Ser	missense	Exon 2 of 3	ENSP00000491188.1	A0A1W2PNZ6
SRPX2	ENST00000638920.1	TSL:5	n.983A>G		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

AF:

0.000402

AC:

AN:

111823

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000572

AC:

105

AN:

183471

AF XY:

0.000383

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000919

AC:

1009

AN:

1098171

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

322

AN XY:

363529

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26400

American (AMR)

AF:

0.0000284

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

54139

European-Finnish (FIN)

AF:

0.000370

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00116

AC:

973

AN:

842091

Other (OTH)

AF:

0.000369

AC:

AN:

46090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

140

186

233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000402

AC:

AN:

111823

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

33993

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30726

American (AMR)

AF:

0.0000946

AC:

AN:

10569

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00

AC:

AN:

2653

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000752

AC:

AN:

53182

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000715

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (4)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.39

REVEL

Benign

0.080

Sift

Benign

0.036

Sift4G

Benign

0.14

Polyphen

0.063

Vest4

0.69

MVP

0.43

MPC

0.13

ClinPred

0.047

GERP RS

5.5

PromoterAI

-0.0070

Neutral

(source)

Varity_R

0.11

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over