rs202093236

Variant names:

• chr2-230873449-G-A
• rs202093236
• NM_030926.6:c.153G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-230873449-G-A
• chr2-230873449-G-C
• chr2-230873449-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_030926.6(ITM2C):​c.153G>A​(p.Arg51Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,606,674 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (21 hom.)
• Consequence: ITM2C NM_030926.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2C	NM_030926.6	c.153G>A	p.Arg51Arg	synonymous_variant	Exon 2 of 6	ENST00000326427.11	NP_112188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2C	ENST00000326427.11	c.153G>A	p.Arg51Arg	synonymous_variant	Exon 2 of 6	1	NM_030926.6	ENSP00000322730.6

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 290 AN: 152232 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00269 AC: 658 AN: 244576 Hom.: 10 AF XY: 0.00257 AC XY: 340 AN XY: 132408

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0254

Gnomad NFE exome AF: 0.000889

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00105 AC: 1534 AN: 1454324 Hom.: 21 Cov.: 29 AF XY: 0.00101 AC XY: 731 AN XY: 723236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.0244

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152350 Hom.: 2 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74506

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000894 Hom.: 0

Bravo AF: 0.000144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

LitVar

Other links and lift over

dbSNP: rs202093236; hg19: chr2-231738164;