chr2-230865053-G-T

Variant names:

• chr2-230865053-G-T
• rs747135256
• NM_030926.6:c.28G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030926.6(ITM2C):​c.28G>T​(p.Val10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,526,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ITM2C NM_030926.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 5 publications found

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]

ENSG00000308773 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10778615).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITM2C	NM_030926.6	MANE Select	c.28G>T	p.Val10Leu	missense	Exon 1 of 6	NP_112188.1	Q9NQX7-1
	ITM2C	NM_001287241.2		c.28G>T	p.Val10Leu	missense	Exon 2 of 7	NP_001274170.1	Q9NQX7-1
	ITM2C	NM_001012516.2		c.28G>T	p.Val10Leu	missense	Exon 1 of 5	NP_001012534.1	Q9NQX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITM2C	ENST00000326427.11	TSL:1 MANE Select	c.28G>T	p.Val10Leu	missense	Exon 1 of 6	ENSP00000322730.6	Q9NQX7-1
	ITM2C	ENST00000326407.10	TSL:1	c.28G>T	p.Val10Leu	missense	Exon 1 of 5	ENSP00000322100.6	Q9NQX7-3
	ITM2C	ENST00000335005.10	TSL:1	c.28G>T	p.Val10Leu	missense	Exon 1 of 5	ENSP00000335121.6	Q9NQX7-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152164 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000557 AC: 9 AN: 161520 AF XY: 0.0000447

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 232 AN: 1374056 Hom.: 0 Cov.: 30 AF XY: 0.000162 AC XY: 110 AN XY: 677022

African (AFR) AF: 0.00 AC: 0 AN: 29044

American (AMR) AF: 0.00 AC: 0 AN: 37222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23974

East Asian (EAS) AF: 0.00 AC: 0 AN: 33240

South Asian (SAS) AF: 0.00 AC: 0 AN: 76834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.000215 AC: 229 AN: 1063454

Other (OTH) AF: 0.0000534 AC: 3 AN: 56204

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74322

African (AFR) AF: 0.0000482 AC: 2 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000253 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.18	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.51	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.91	P
Vest4		0.23
MutPred		0.18		Loss of methylation at K14 (P = 0.0766)
MVP		0.48
MPC		0.34
ClinPred		0.16	T
GERP RS		3.3
PromoterAI		-0.066	Neutral
Varity_R		0.097
gMVP		0.44
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs747135256; hg19: chr2-231729768;