NM_181507.2:c.1511-30G>A

Variant names:

• chr11-18296152-C-T
• rs2305565
• NM_181507.2:c.1511-30G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_181507.2(HPS5):​c.1511-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,603,210 control chromosomes in the GnomAD database, including 295,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26485 hom., cov: 32)
  • Exomes 𝑓: 0.61 (268522 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.152
• Publications: 13 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-18296152-C-T is Benign according to our data. Variant chr11-18296152-C-T is described in ClinVar as Benign. ClinVar VariationId is 262983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181507.2. 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
	HPS5	NM_181507.2	MANE Select	c.1511-30G>A		intron	N/A	NP_852608.1
	HPS5	NM_001440902.1		c.1511-30G>A		intron	N/A	NP_001427831.1
	HPS5	NM_001440903.1		c.1511-30G>A		intron	N/A	NP_001427832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS5	ENST00000349215.8	TSL:1 MANE Select	c.1511-30G>A		intron	N/A	ENSP00000265967.5
	HPS5	ENST00000396253.7	TSL:1	c.1169-30G>A		intron	N/A	ENSP00000379552.3
	HPS5	ENST00000438420.6	TSL:1	c.1169-30G>A		intron	N/A	ENSP00000399590.2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89117 AN: 151844 Hom.: 26449 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.560

GnomAD2 exomes AF: 0.594 AC: 148002 AN: 249122 AF XY: 0.590

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.598

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.858

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.605 AC: 878169 AN: 1451248 Hom.: 268522 Cov.: 30 AF XY: 0.603 AC XY: 435357 AN XY: 722540

African (AFR) AF: 0.566 AC: 18818 AN: 33220

American (AMR) AF: 0.597 AC: 26650 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11993 AN: 26050

East Asian (EAS) AF: 0.809 AC: 32026 AN: 39564

South Asian (SAS) AF: 0.594 AC: 51035 AN: 85966

European-Finnish (FIN) AF: 0.553 AC: 29310 AN: 52960

Middle Eastern (MID) AF: 0.386 AC: 2219 AN: 5754

European-Non Finnish (NFE) AF: 0.608 AC: 670227 AN: 1103048

Other (OTH) AF: 0.598 AC: 35891 AN: 60056

GnomAD4 genome AF: 0.587 AC: 89206 AN: 151962 Hom.: 26485 Cov.: 32 AF XY: 0.587 AC XY: 43628 AN XY: 74264

African (AFR) AF: 0.574 AC: 23790 AN: 41458

American (AMR) AF: 0.589 AC: 8989 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4387 AN: 5168

South Asian (SAS) AF: 0.621 AC: 2988 AN: 4812

European-Finnish (FIN) AF: 0.545 AC: 5743 AN: 10540

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39720 AN: 67942

Other (OTH) AF: 0.565 AC: 1193 AN: 2110

Alfa AF: 0.483 Hom.: 2545

Bravo AF: 0.592

Asia WGS AF: 0.747 AC: 2592 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

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

Hermansky-Pudlak syndrome 5 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: 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	-0.44
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		-0.15
PromoterAI		-0.015	Neutral
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2305565; hg19: chr11-18317699;