1-84939543-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153259.4(MCOLN2):c.1110+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,612,854 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (112 hom.)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.61

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-84939543-C-T is Benign according to our data. Variant chr1-84939543-C-T is described in ClinVar as [Benign]. Clinvar id is 777913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCOLN2	NM_153259.4	c.1110+10G>A		intron_variant		ENST00000370608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN2	ENST00000370608.8	c.1110+10G>A		intron_variant		1	NM_153259.4
MCOLN2	ENST00000531325.5	n.1351+10G>A		intron_variant, non_coding_transcript_variant		1
MCOLN2	ENST00000284027.5	c.1026+10G>A		intron_variant		5		P1
MCOLN2	ENST00000463065.5	c.*45-1461G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3272 AN: 152092 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00557 AC: 1393 AN: 250270 Hom.: 43 AF XY: 0.00398 AC XY: 538 AN XY: 135264

Gnomad AFR exome AF: 0.0754

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00361

GnomAD4 exome AF: 0.00220 AC: 3211 AN: 1460644 Hom.: 112 Cov.: 31 AF XY: 0.00183 AC XY: 1332 AN XY: 726630

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000981

Gnomad4 OTH exome AF: 0.00461

GnomAD4 genome AF: 0.0216 AC: 3283 AN: 152210 Hom.: 122 Cov.: 32 AF XY: 0.0209 AC XY: 1554 AN XY: 74438

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.00805

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0159 Hom.: 24

Bravo AF: 0.0241

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.087
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs74670650; hg19: chr1-85405226;