dbSNP rs1551305: TPCN2:c.2181-110G>A (chr11-69087765-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

16 publications found

Variant links:

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

TPCN2 links:

ENSG00000287725 (HGNC:):

ENSG00000287725 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPCN2	NM_139075.4 link	c.2181-110G>A		intron_variant	Intron 24 of 24	ENST00000294309.8	NP_620714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPCN2	ENST00000294309.8 link	c.2181-110G>A		intron_variant	Intron 24 of 24	1	NM_139075.4	ENSP00000294309.3
ENSG00000287725	ENST00000637084.1 link	n.1038-110G>A		intron_variant	Intron 12 of 14	1		ENSP00000490615.1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68101

AN:

151938

Hom.:

15684

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7120

14239

21359

28478

35598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2990

5980

8970

11960

14950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.448

AC:

68113

AN:

152056

Hom.:

15684

Cov.:

AF XY:

0.440

AC XY:

32686

AN XY:

74336

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1921

3842

5764

7685

9606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

(source)

DANN

Benign

0.77

PhyloP100

-0.061

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over