chr11-69087765-G-A

Variant names:

• chr11-69087765-G-A
• rs1551305
• NM_139075.4:c.2181-110G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139075.4(TPCN2):​c.2181-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 780,160 control chromosomes in the GnomAD database, including 79,865 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15684 hom., cov: 32)
  • Exomes 𝑓: 0.44 (64181 hom.)
• Consequence: TPCN2 NM_139075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 16 publications found

Genes affected

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

TPCN2 Gene-Disease associations (from GenCC):

• albinism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000287725 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139075.4. 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
	TPCN2	NM_139075.4	MANE Select	c.2181-110G>A		intron	N/A	NP_620714.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPCN2	ENST00000294309.8	TSL:1 MANE Select	c.2181-110G>A		intron	N/A	ENSP00000294309.3
	ENSG00000287725	ENST00000637084.1	TSL:1	n.1038-110G>A		intron	N/A	ENSP00000490615.1
	TPCN2	ENST00000637342.1	TSL:5	c.2003+1835G>A		intron	N/A	ENSP00000490171.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68101 AN: 151938 Hom.: 15684 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.443 AC: 278517 AN: 628104 Hom.: 64181 AF XY: 0.436 AC XY: 142020 AN XY: 325592

African (AFR) AF: 0.400 AC: 6592 AN: 16476

American (AMR) AF: 0.329 AC: 7696 AN: 23408

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 7793 AN: 16104

East Asian (EAS) AF: 0.307 AC: 9790 AN: 31872

South Asian (SAS) AF: 0.235 AC: 12557 AN: 53462

European-Finnish (FIN) AF: 0.477 AC: 20922 AN: 43860

Middle Eastern (MID) AF: 0.399 AC: 1286 AN: 3222

European-Non Finnish (NFE) AF: 0.484 AC: 197570 AN: 407822

Other (OTH) AF: 0.449 AC: 14311 AN: 31878

GnomAD4 genome AF: 0.448 AC: 68113 AN: 152056 Hom.: 15684 Cov.: 32 AF XY: 0.440 AC XY: 32686 AN XY: 74336

African (AFR) AF: 0.407 AC: 16889 AN: 41460

American (AMR) AF: 0.392 AC: 5995 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1543 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4824

European-Finnish (FIN) AF: 0.480 AC: 5076 AN: 10580

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34111 AN: 67944

Other (OTH) AF: 0.459 AC: 970 AN: 2114

Alfa AF: 0.321 Hom.: 856

Bravo AF: 0.446

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		-0.061
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: rs1551305; hg19: chr11-68855233;