rs5920818

Variant names:

• chrX-100314162-A-G
• rs5920818
• NM_001184880.2:c.2849-17287T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184880.2(PCDH19):​c.2849-17287T>C variant causes a intron change. The variant allele was found at a frequency of 0.329 in 110,922 control chromosomes in the GnomAD database, including 5,371 homozygotes. There are 11,094 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 0.33 (5371 hom., 11094 hem., cov: 23)
• Consequence: PCDH19 NM_001184880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34
• Publications: 1 publications found

Genes affected

PCDH19 (HGNC:14270): (protocadherin 19) The protein encoded by this gene is a member of the delta-2 protocadherin subclass of the cadherin superfamily. The encoded protein is thought to be a calcium-dependent cell-adhesion protein that is primarily expressed in the brain. Mutations in this gene on human chromosome X are associated with sporadic infantile epileptic encephalopathy and to a female-restricted form of epilepsy (EFMR; also known as PCDH19RE). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

PCDH19 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 9

  Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH19	NM_001184880.2	c.2849-17287T>C		intron_variant	Intron 5 of 5	ENST00000373034.8	NP_001171809.1
PCDH19	NM_001105243.2	c.2708-17287T>C		intron_variant	Intron 4 of 4		NP_001098713.1
PCDH19	NM_020766.3	c.2705-17287T>C		intron_variant	Intron 4 of 4		NP_065817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH19	ENST00000373034.8	c.2849-17287T>C		intron_variant	Intron 5 of 5	1	NM_001184880.2	ENSP00000362125.4
PCDH19	ENST00000255531.8	c.2708-17287T>C		intron_variant	Intron 4 of 4	1		ENSP00000255531.7
PCDH19	ENST00000420881.6	c.2705-17287T>C		intron_variant	Intron 4 of 4	1		ENSP00000400327.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 36511 AN: 110871 Hom.: 5378 Cov.: 23

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.329 AC: 36499 AN: 110922 Hom.: 5371 Cov.: 23 AF XY: 0.334 AC XY: 11094 AN XY: 33194

African (AFR) AF: 0.0667 AC: 2051 AN: 30755

American (AMR) AF: 0.313 AC: 3274 AN: 10459

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1056 AN: 2636

East Asian (EAS) AF: 0.650 AC: 2251 AN: 3462

South Asian (SAS) AF: 0.551 AC: 1443 AN: 2619

European-Finnish (FIN) AF: 0.507 AC: 2966 AN: 5855

Middle Eastern (MID) AF: 0.358 AC: 77 AN: 215

European-Non Finnish (NFE) AF: 0.426 AC: 22457 AN: 52734

Other (OTH) AF: 0.357 AC: 539 AN: 1511

Alfa AF: 0.413 Hom.: 13824

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Benign	0.71
PhyloP100		5.3
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: rs5920818; hg19: chrX-99569160;