chr2-230877483-G-T

Variant names:

• chr2-230877483-G-T
• rs35154063
• NM_030926.6:c.645G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030926.6(ITM2C):​c.645G>T​(p.Gly215Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,040 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (16 hom.)
• Consequence: ITM2C NM_030926.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.423
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 2-230877483-G-T is Benign according to our data. Variant chr2-230877483-G-T is described in ClinVar as Benign. ClinVar VariationId is 775830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.423 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00761 (1159/152332) while in subpopulation AFR AF = 0.0267 (1111/41566). AF 95% confidence interval is 0.0254. There are 18 homozygotes in GnomAd4. There are 561 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.645G>T	p.Gly215Gly	synonymous	Exon 5 of 6	NP_112188.1	Q9NQX7-1
	ITM2C	NM_001287241.2		c.645G>T	p.Gly215Gly	synonymous	Exon 6 of 7	NP_001274170.1	Q9NQX7-1
	ITM2C	NM_001012516.2		c.534G>T	p.Gly178Gly	synonymous	Exon 4 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.645G>T	p.Gly215Gly	synonymous	Exon 5 of 6	ENSP00000322730.6	Q9NQX7-1
	ITM2C	ENST00000326407.10	TSL:1	c.534G>T	p.Gly178Gly	synonymous	Exon 4 of 5	ENSP00000322100.6	Q9NQX7-3
	ITM2C	ENST00000335005.10	TSL:1	c.504G>T	p.Gly168Gly	synonymous	Exon 4 of 5	ENSP00000335121.6	Q9NQX7-2

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152214 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

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: 0.0000147

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00185 AC: 464 AN: 251358 AF XY: 0.00142

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000763 AC: 1116 AN: 1461708 Hom.: 16 Cov.: 33 AF XY: 0.000648 AC XY: 471 AN XY: 727174

African (AFR) AF: 0.0277 AC: 928 AN: 33480

American (AMR) AF: 0.000693 AC: 31 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5758

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111936

Other (OTH) AF: 0.00157 AC: 95 AN: 60394

GnomAD4 genome AF: 0.00761 AC: 1159 AN: 152332 Hom.: 18 Cov.: 32 AF XY: 0.00753 AC XY: 561 AN XY: 74500

African (AFR) AF: 0.0267 AC: 1111 AN: 41566

American (AMR) AF: 0.00203 AC: 31 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00368 Hom.: 3

Bravo AF: 0.00843

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		0.42
Mutation Taster		=96/4	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: rs35154063; hg19: chr2-231742198;