rs1044833

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 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 benign 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
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385503.1. 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
	CAPRIN2	NM_001385503.1	MANE Select	c.2570-1G>T		splice_acceptor intron	N/A	NP_001372432.1	F5H5J8
	CAPRIN2	NM_001385516.1		c.2859G>T	p.Gln953His	missense	Exon 18 of 18	NP_001372445.1
	CAPRIN2	NM_032156.5		c.2856G>T	p.Gln952His	missense	Exon 18 of 18	NP_115532.3	Q6IMN6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPRIN2	ENST00000417045.5	TSL:1	c.2856G>T	p.Gln952His	missense	Exon 18 of 18	ENSP00000391479.1	Q6IMN6-3
	CAPRIN2	ENST00000395805.6	TSL:1	c.2691G>T	p.Gln897His	missense	Exon 17 of 17	ENSP00000379150.2	Q6IMN6-10
	CAPRIN2	ENST00000695402.1	MANE Select	c.2570-1G>T		splice_acceptor intron	N/A	ENSP00000511883.1	F5H5J8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
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
PhyloP100		3.2
ClinPred		0.91	D
GERP RS		4.9
Mutation Taster		=4/96	disease causing

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

Other links and lift over

dbSNP: rs1044833; hg19: chr12-30863405;