rs36224186

chrX-100664569-C-AchrX-100664569-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014467.3(SRPX2):c.356-205C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 111,259 control chromosomes in the GnomAD database, including 899 homozygotes. There are 2,801 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.089 (899 hom., 2801 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-100664569-C-A is Benign according to our data. Variant chrX-100664569-C-A is described in ClinVar as [Benign]. Clinvar id is 1229905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPX2	NM_014467.3	c.356-205C>A		intron_variant		ENST00000373004.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPX2	ENST00000373004.5	c.356-205C>A		intron_variant		1	NM_014467.3	P1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 9851 AN: 111209 Hom.: 895 Cov.: 23 AF XY: 0.0830 AC XY: 2776 AN XY: 33435

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.000673

Gnomad MID AF: 0.0504

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.0673

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0888 AC: 9882 AN: 111259 Hom.: 899 Cov.: 23 AF XY: 0.0836 AC XY: 2801 AN XY: 33495

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.000673

Gnomad4 NFE AF: 0.00504

Gnomad4 OTH AF: 0.0698

Alfa AF: 0.0639 Hom.: 253

Bravo AF: 0.101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.14
Dann	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs36224186; hg19: chrX-99919566;