Variant 2-230877499-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_030926.6(ITM2C):c.661C>T(p.Leu221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,048 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 78 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 81 hom. )

Consequence

ITM2C
NM_030926.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-230877499-C-T is Benign according to our data. Variant chr2-230877499-C-T is described in ClinVar as [Benign]. Clinvar id is 791896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITM2C	NM_030926.6 linkuse as main transcript	c.661C>T	p.Leu221=	synonymous_variant	5/6	ENST00000326427.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITM2C	ENST00000326427.11 linkuse as main transcript	c.661C>T	p.Leu221=	synonymous_variant	5/6	1	NM_030926.6	P1	Q9NQX7-1
ITM2C	ENST00000326407.10 linkuse as main transcript	c.550C>T	p.Leu184=	synonymous_variant	4/5	1			Q9NQX7-3
ITM2C	ENST00000335005.10 linkuse as main transcript	c.520C>T	p.Leu174=	synonymous_variant	4/5	1			Q9NQX7-2
ITM2C	ENST00000409704.6 linkuse as main transcript	c.475C>T	p.Leu159=	synonymous_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2818

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00791

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00596

AC:

1497

AN:

251350

Hom.:

AF XY:

0.00499

AC XY:

678

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0616

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00262

AC:

3832

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1809

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0631

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000329

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.0186

AC:

2838

AN:

152322

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1339

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0617

Gnomad4 AMR

AF:

0.00790

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00649

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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