Genetic Variant ITM2C:p.Ile13Val (chr2-230865062-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_030926.6(ITM2C):c.37A>G(p.Ile13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,534,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ITM2C
NM_030926.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.325

Publications

0 publications found

Variant links:

Genes affected

ITM2C (HGNC:6175): (integral membrane protein 2C) Enables amyloid-beta binding activity. Involved in negative regulation of neuron projection development and neuron differentiation. Located in several cellular components, including Golgi apparatus; lysosome; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ITM2C links:

ENSG00000308773 (HGNC:):

ENSG00000308773 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01976803).

BP6

Variant 2-230865062-A-G is Benign according to our data. Variant chr2-230865062-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3530814.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030926.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITM2C	NM_030926.6	MANE Select	c.37A>G	p.Ile13Val	missense	Exon 1 of 6	NP_112188.1	Q9NQX7-1
ITM2C	NM_001287241.2		c.37A>G	p.Ile13Val	missense	Exon 2 of 7	NP_001274170.1	Q9NQX7-1
ITM2C	NM_001012516.2		c.37A>G	p.Ile13Val	missense	Exon 1 of 5	NP_001012534.1	Q9NQX7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITM2C	ENST00000326427.11	TSL:1 MANE Select	c.37A>G	p.Ile13Val	missense	Exon 1 of 6	ENSP00000322730.6	Q9NQX7-1
ITM2C	ENST00000326407.10	TSL:1	c.37A>G	p.Ile13Val	missense	Exon 1 of 5	ENSP00000322100.6	Q9NQX7-3
ITM2C	ENST00000335005.10	TSL:1	c.37A>G	p.Ile13Val	missense	Exon 1 of 5	ENSP00000335121.6	Q9NQX7-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000182

AC:

AN:

164916

AF XY:

0.0000220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000285

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000181

AC:

AN:

1382720

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

682450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29312

American (AMR)

AF:

0.00

AC:

AN:

37680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24122

East Asian (EAS)

AF:

0.000622

AC:

AN:

33738

South Asian (SAS)

AF:

0.00

AC:

AN:

77278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1069664

Other (OTH)

AF:

0.0000353

AC:

AN:

56614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000540

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000169

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.0

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.57

M_CAP

Benign

0.030

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-0.33

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.15

REVEL

Benign

0.047

Sift

Benign

1.0

Sift4G

Benign

0.97

Polyphen

0.0

Vest4

0.048

MutPred

0.30

Loss of helix (P = 0.0068)

MVP

0.12

MPC

0.20

ClinPred

0.0082

GERP RS

-5.1

PromoterAI

0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.025

gMVP

0.23

Mutation Taster

=95/5

polymorphism

(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