Variant rs1338518342 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001184880.2(PCDH19):c.789C>T(p.Ser263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,211,171 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: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

PCDH19
NM_001184880.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.90

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-100407809-G-A is Benign according to our data. Variant chrX-100407809-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465309.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.9 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCDH19	NM_001184880.2 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/6	ENST00000373034.8
PCDH19	NM_001105243.2 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/5
PCDH19	NM_020766.3 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH19	ENST00000373034.8 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/6	1	NM_001184880.2	A1	Q8TAB3-1
PCDH19	ENST00000255531.8 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/5	1		P5	Q8TAB3-2
PCDH19	ENST00000420881.6 linkuse as main transcript	c.789C>T	p.Ser263=	synonymous_variant	1/5	1		A1	Q8TAB3-3

Frequencies

GnomAD3 genomes

AF:

0.00000885

AC:

AN:

113046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35184

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1098125

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363481

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000885

AC:

AN:

113046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35184

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.0

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over