11-18292882-T-G

Variant names:

• chr11-18292882-T-G
• rs111497919
• NM_181507.2:c.1862+17A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181507.2(HPS5):​c.1862+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,597,632 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (87 hom., cov: 32)
  • Exomes 𝑓: 0.017 (296 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.284
• Publications: 2 publications found

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]

HPS5 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-18292882-T-G is Benign according to our data. Variant chr11-18292882-T-G is described in ClinVar as Benign. ClinVar VariationId is 262984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS5	NM_181507.2	c.1862+17A>C		intron_variant	Intron 15 of 22	ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.1862+17A>C		intron_variant	Intron 15 of 22	1	NM_181507.2	ENSP00000265967.5

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4120 AN: 152190 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0180 AC: 4516 AN: 251432 AF XY: 0.0169

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0393

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0198

Gnomad NFE exome AF: 0.0191

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0172 AC: 24811 AN: 1445324 Hom.: 296 Cov.: 28 AF XY: 0.0167 AC XY: 12045 AN XY: 720194

African (AFR) AF: 0.0533 AC: 1765 AN: 33090

American (AMR) AF: 0.0128 AC: 572 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0385 AC: 1004 AN: 26048

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39626

South Asian (SAS) AF: 0.00343 AC: 295 AN: 85956

European-Finnish (FIN) AF: 0.0189 AC: 1010 AN: 53406

Middle Eastern (MID) AF: 0.0195 AC: 112 AN: 5740

European-Non Finnish (NFE) AF: 0.0172 AC: 18904 AN: 1096902

Other (OTH) AF: 0.0192 AC: 1147 AN: 59850

GnomAD4 genome AF: 0.0271 AC: 4125 AN: 152308 Hom.: 87 Cov.: 32 AF XY: 0.0264 AC XY: 1968 AN XY: 74488

African (AFR) AF: 0.0537 AC: 2233 AN: 41554

American (AMR) AF: 0.0182 AC: 279 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 68030

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0132 Hom.: 7

Bravo AF: 0.0278

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 17, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.55
PhyloP100		0.28
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: rs111497919; hg19: chr11-18314429;