chr20-44114565-A-AGT

Position:

• chr20-44114565-A-AGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020433.5(JPH2):​c.*14+216_*14+217insAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.039 (123 hom., cov: 0)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794

Genes affected

JPH2 (HGNC:14202): (junctophilin 2) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-44114565-A-AGT is Benign according to our data. Variant chr20-44114565-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1246902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH2	NM_020433.5	c.*14+216_*14+217insAC		intron_variant		ENST00000372980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+216_*14+217insAC		intron_variant		5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5568 AN: 141784 Hom.: 123 Cov.: 0

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0651

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0393 AC: 5572 AN: 141882 Hom.: 123 Cov.: 0 AF XY: 0.0404 AC XY: 2761 AN XY: 68330

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0362

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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3037626; hg19: chr20-42743205;