Genetic Variant MCOLN2:c.1110+10G>A (chr1-84939543-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.61

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 777913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN2	NM_153259.4	MANE Select	c.1110+10G>A		intron	N/A	NP_694991.2
	MCOLN2	NM_001330647.2		c.1026+10G>A		intron	N/A	NP_001317576.1	Q8IZK6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCOLN2	ENST00000370608.8	TSL:1 MANE Select	c.1110+10G>A	intron	N/A	ENSP00000359640.3	Q8IZK6-1
MCOLN2	ENST00000531325.5	TSL:1	n.1351+10G>A	intron	N/A
MCOLN2	ENST00000945493.1		c.1110+10G>A	intron	N/A	ENSP00000615552.1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3272

AN:

152092

Hom.:

123

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00557

AC:

1393

AN:

250270

AF XY:

0.00398

show subpopulations

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 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.:

AF XY:

0.00183

AC XY:

1332

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.0783

AC:

2612

AN:

33350

American (AMR)

AF:

0.00402

AC:

178

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000163

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00348

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000981

AC:

109

AN:

1111582

Other (OTH)

AF:

0.00461

AC:

278

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

137

274

411

548

685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0216

AC:

3283

AN:

152210

Hom.:

122

Cov.:

AF XY:

0.0209

AC XY:

1554

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0747

AC:

3098

AN:

41494

American (AMR)

AF:

0.00805

AC:

123

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68034

Other (OTH)

AF:

0.0185

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

150

300

450

600

750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0139

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.087

(source)

DANN

Benign

0.60

PhyloP100

-2.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over