Variant 1-84937887-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153259.4(MCOLN2):c.1213-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,614,142 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 15 hom. )

Consequence

MCOLN2
NM_153259.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001299

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.318

Variant links:

Genes affected

MCOLN2 (HGNC:13357): (mucolipin TRP cation channel 2) Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]

MCOLN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-84937887-A-T is Benign according to our data. Variant chr1-84937887-A-T is described in ClinVar as [Benign]. Clinvar id is 711275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00796 (1213/152366) while in subpopulation AFR AF= 0.0273 (1137/41582). AF 95% confidence interval is 0.026. There are 15 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCOLN2	NM_153259.4 linkuse as main transcript	c.1213-10T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370608.8	NP_694991.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MCOLN2	ENST00000370608.8 linkuse as main transcript	c.1213-10T>A	splice_polypyrimidine_tract_variant, intron_variant	1	NM_153259.4	ENSP00000359640		Q8IZK6-1
MCOLN2	ENST00000531325.5 linkuse as main transcript	n.1454-10T>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
MCOLN2	ENST00000284027.5 linkuse as main transcript	c.1129-10T>A	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000284027	P1	Q8IZK6-2
MCOLN2	ENST00000463065.5 linkuse as main transcript	c.*147-10T>A	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	2		ENSP00000436299

Frequencies

GnomAD3 genomes

AF:

0.00794

AC:

1209

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00210

AC:

528

AN:

250998

Hom.:

AF XY:

0.00147

AC XY:

200

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000787

AC:

1151

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

473

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00796

AC:

1213

AN:

152366

Hom.:

Cov.:

AF XY:

0.00741

AC XY:

552

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00884

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over