chr11-69087765-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_139075.4(TPCN2):​c.2181-110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000793 in 630,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 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: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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>C		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>C		intron	N/A	ENSP00000294309.3
	ENSG00000287725	ENST00000637084.1	TSL:1	n.1038-110G>C		intron	N/A	ENSP00000490615.1
	TPCN2	ENST00000637342.1	TSL:5	c.2003+1835G>C		intron	N/A	ENSP00000490171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000793 AC: 5 AN: 630202 Hom.: 0 AF XY: 0.0000122 AC XY: 4 AN XY: 326658

African (AFR) AF: 0.00 AC: 0 AN: 16508

American (AMR) AF: 0.00 AC: 0 AN: 23444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16142

East Asian (EAS) AF: 0.00 AC: 0 AN: 31904

South Asian (SAS) AF: 0.00 AC: 0 AN: 53536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3238

European-Non Finnish (NFE) AF: 0.0000122 AC: 5 AN: 409488

Other (OTH) AF: 0.00 AC: 0 AN: 31966

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		-0.061

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;