rs1555984464

Variant names:

• chrX-100402721-G-A
• rs1555984464
• NM_001184880.2:c.2419C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-100402721-G-A
• chrX-100402721-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001184880.2(PCDH19):​c.2419C>T​(p.Leu807Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000182 in 1,097,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: PCDH19 NM_001184880.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.55
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant X-100402721-G-A is Benign according to our data. Variant chrX-100402721-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465299.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184880.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH19	NM_001184880.2	MANE Select	c.2419C>T	p.Leu807Leu	synonymous	Exon 3 of 6	NP_001171809.1
	PCDH19	NM_001105243.2		c.2278C>T	p.Leu760Leu	synonymous	Exon 2 of 5	NP_001098713.1
	PCDH19	NM_020766.3		c.2278C>T	p.Leu760Leu	synonymous	Exon 2 of 5	NP_065817.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH19	ENST00000373034.8	TSL:1 MANE Select	c.2419C>T	p.Leu807Leu	synonymous	Exon 3 of 6	ENSP00000362125.4
	PCDH19	ENST00000255531.8	TSL:1	c.2278C>T	p.Leu760Leu	synonymous	Exon 2 of 5	ENSP00000255531.7
	PCDH19	ENST00000420881.6	TSL:1	c.2278C>T	p.Leu760Leu	synonymous	Exon 2 of 5	ENSP00000400327.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097725 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363079

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.0000568 AC: 2 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841673

Other (OTH) AF: 0.00 AC: 0 AN: 46082

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 9 Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.70
PhyloP100		5.6

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: rs1555984464; hg19: chrX-99657719; COSMIC: COSV99720818;