rs2305564

Positions:

• chr11-18295911-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181507.2(HPS5):​c.1634+88A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,383,236 control chromosomes in the GnomAD database, including 198,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17969 hom., cov: 32)
  • Exomes 𝑓: 0.54 (180508 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.166

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-18295911-T-A is Benign according to our data. Variant chr11-18295911-T-A is described in ClinVar as [Benign]. Clinvar id is 1263434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS5	NM_181507.2	c.1634+88A>T		intron_variant		ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.1634+88A>T		intron_variant		1	NM_181507.2	ENSP00000265967	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72576 AN: 151934 Hom.: 17953 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.537 AC: 661099 AN: 1231184 Hom.: 180508 AF XY: 0.533 AC XY: 332444 AN XY: 623718

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.478 AC: 72638 AN: 152052 Hom.: 17969 Cov.: 32 AF XY: 0.477 AC XY: 35444 AN XY: 74310

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.445

Alfa AF: 0.499 Hom.: 2424

Bravo AF: 0.472

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2305564; hg19: chr11-18317458; COSMIC: COSV61687995; COSMIC: COSV61687995;