NM_001385503.1:c.2786G>T

Variant names:

• chr12-30710254-C-A
• rs368158820
• NM_001385503.1:c.2786G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385503.1(CAPRIN2):​c.2786G>T​(p.Gly929Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: CAPRIN2 NM_001385503.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71

Genes affected

CAPRIN2 (HGNC:21259): (caprin family member 2) The protein encoded by this gene may regulate the transport of mRNA. It may play a role in the differentiation of erythroblasts. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

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
CAPRIN2	NM_001385503.1	c.2786G>T	p.Gly929Val	missense_variant	Exon 19 of 19	ENST00000695402.1	NP_001372432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN2	ENST00000695402.1	c.2786G>T	p.Gly929Val	missense_variant	Exon 19 of 19		NM_001385503.1	ENSP00000511883.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251136 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135718

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: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000944 AC: 138 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 66 AN XY: 727238

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000120

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3032G>T (p.G1011V) alteration is located in exon 18 (coding exon 18) of the CAPRIN2 gene. This alteration results from a G to T substitution at nucleotide position 3032, causing the glycine (G) at amino acid position 1011 to be replaced by a valine (V). 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
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.026	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.45
MVP		0.72
MPC		0.40
ClinPred		0.81	D
GERP RS		5.8
gMVP		0.83

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: rs368158820; hg19: chr12-30863188;