10-46550030-C-T

Variant names:

• chr10-46550030-C-T
• rs782694278
• NM_001385282.1:c.707G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385282.1(GPRIN2):​c.707G>A​(p.Cys236Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 76)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.468
• Publications: 0 publications found

Genes affected

GPRIN2 (HGNC:23730): (G protein regulated inducer of neurite outgrowth 2) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385282.1. 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
	GPRIN2	NM_001385282.1	MANE Select	c.707G>A	p.Cys236Tyr	missense	Exon 3 of 3	NP_001372211.1	O60269
	GPRIN2	NM_001385287.1		c.779G>A	p.Cys260Tyr	missense	Exon 4 of 4	NP_001372216.1
	GPRIN2	NM_001385289.1		c.779G>A	p.Cys260Tyr	missense	Exon 4 of 4	NP_001372218.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRIN2	ENST00000374314.6	TSL:6 MANE Select	c.707G>A	p.Cys236Tyr	missense	Exon 3 of 3	ENSP00000363433.4	O60269
	GPRIN2	ENST00000374317.2	TSL:3	c.707G>A	p.Cys236Tyr	missense	Exon 3 of 3	ENSP00000363436.1	O60269
	GPRIN2	ENST00000889306.1		c.707G>A	p.Cys236Tyr	missense	Exon 4 of 4	ENSP00000559365.1

Frequencies

GnomAD3 genomes Cov.: 76

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250986 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461540 Hom.: 0 Cov.: 112 AF XY: 0.00000413 AC XY: 3 AN XY: 727090

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000179 AC: 8 AN: 44716

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 76

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	0.21
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.57
DEOGEN2	Benign	0.037	T
LIST_S2	Benign	0.46	T
MetaRNN	Uncertain	0.62	D
PhyloP100		0.47
PROVEAN	Uncertain	-2.8	D
Sift	Benign	0.042	D
Sift4G	Benign	0.11	T
Vest4		0.56
gMVP		0.74

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: rs782694278; hg19: chr10-46999587;