rs1044833

Variant names:

• chr12-30710471-C-A
• rs1044833
• ENST00000417045.5:c.2856G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001385503.1(CAPRIN2):​c.2570-1G>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPRIN2 NM_001385503.1 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.29254302 fraction of the gene.
• 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.2570-1G>T		splice_acceptor_variant, intron_variant	Intron 18 of 18	ENST00000695402.1	NP_001372432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN2	ENST00000695402.1	c.2570-1G>T		splice_acceptor_variant, intron_variant	Intron 18 of 18		NM_001385503.1	ENSP00000511883.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.051
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0050	T
ClinPred		0.91	D
GERP RS		4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.62		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1044833; hg19: chr12-30863405;