12-30716621-G-A

Position:

• chr12-30716621-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385503.1(CAPRIN2):​c.2108C>T​(p.Ser703Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPRIN2 NM_001385503.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31543958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPRIN2	NM_001385503.1	c.2108C>T	p.Ser703Phe	missense_variant	15/19	ENST00000695402.1	NP_001372432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPRIN2	ENST00000695402.1	c.2108C>T	p.Ser703Phe	missense_variant	15/19		NM_001385503.1	ENSP00000511883	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.2351C>T (p.S784F) alteration is located in exon 14 (coding exon 14) of the CAPRIN2 gene. This alteration results from a C to T substitution at nucleotide position 2351, causing the serine (S) at amino acid position 784 to be replaced by a phenylalanine (F). 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	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.3	.;.;.;M
MutationTaster	Benign	0.81	D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.038	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.99, 0.99	.;D;.;D
Vest4		0.40, 0.39, 0.45
MutPred		0.28		.;.;.;Gain of catalytic residue at Y786 (P = 0.0076);
MVP		0.69
MPC		0.19
ClinPred		0.97	D
GERP RS		4.8
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-30869555;