10-46550030-C-T

Variant names:

• chr10-46550030-C-T
• rs1832508242
• NM_001385282.1:c.707G>A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN2	NM_001385282.1	c.707G>A	p.Cys236Tyr	missense_variant	Exon 3 of 3	ENST00000374314.6	NP_001372211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRIN2	ENST00000374314.6	c.707G>A	p.Cys236Tyr	missense_variant	Exon 3 of 3	6	NM_001385282.1	ENSP00000363433.4
GPRIN2	ENST00000374317.2	c.707G>A	p.Cys236Tyr	missense_variant	Exon 3 of 3	3		ENSP00000363436.1

Frequencies

GnomAD3 genomes Cov.: 76

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 76

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.707G>A (p.C236Y) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a G to A substitution at nucleotide position 707, causing the cysteine (C) at amino acid position 236 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
LIST_S2	Benign	0.46	.;T
MetaRNN	Uncertain	0.62	D;D
PROVEAN	Uncertain	-2.8	D;D
Sift	Benign	0.042	D;D
Sift4G	Benign	0.11	T;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

Publications

LitVar

Other links and lift over

dbSNP: rs1832508242; hg19: chr10-46999587;