rs36224185

Variant names:

• chrX-100655157-C-G
• rs36224185
• NM_014467.3:c.163+4292C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014467.3(SRPX2):​c.163+4292C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 112,230 control chromosomes in the GnomAD database, including 7 homozygotes. There are 236 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0074 (7 hom., 236 hem., cov: 22)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00741 (832/112230) while in subpopulation AFR AF = 0.0251 (774/30883). AF 95% confidence interval is 0.0236. There are 7 homozygotes in GnomAd4. There are 236 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High AC in GnomAd4 at 832 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.163+4292C>G		intron_variant	Intron 3 of 10	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.163+4292C>G		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 828 AN: 112177 Hom.: 7 Cov.: 22

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

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: 0.0000563

Gnomad OTH AF: 0.00199

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

GnomAD4 genome AF: 0.00741 AC: 832 AN: 112230 Hom.: 7 Cov.: 22 AF XY: 0.00686 AC XY: 236 AN XY: 34410

African (AFR) AF: 0.0251 AC: 774 AN: 30883

American (AMR) AF: 0.00490 AC: 52 AN: 10612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53286

Other (OTH) AF: 0.00196 AC: 3 AN: 1528

Alfa AF: 0.00612 Hom.: 22

Bravo AF: 0.00853

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36224185; hg19: chrX-99910154;