12-30710321-C-G

Variant names:

• chr12-30710321-C-G
• rs150951809
• NM_001385503.1:c.2719G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385503.1(CAPRIN2):​c.2719G>C​(p.Val907Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V907I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAPRIN2 NM_001385503.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09212816).

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.2719G>C	p.Val907Leu	missense	Exon 19 of 19	NP_001372432.1	F5H5J8
	CAPRIN2	NM_001002259.3		c.2965G>C	p.Val989Leu	missense	Exon 18 of 18	NP_001002259.1	Q6IMN6-1
	CAPRIN2	NM_001319843.2		c.2962G>C	p.Val988Leu	missense	Exon 18 of 18	NP_001306772.1	Q6IMN6-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPRIN2	ENST00000695402.1	MANE Select	c.2719G>C	p.Val907Leu	missense	Exon 19 of 19	ENSP00000511883.1	F5H5J8
	CAPRIN2	ENST00000298892.9	TSL:1	c.2815G>C	p.Val939Leu	missense	Exon 17 of 17	ENSP00000298892.5	Q6IMN6-2
	CAPRIN2	ENST00000395805.6	TSL:1	c.*123G>C		3_prime_UTR	Exon 17 of 17	ENSP00000379150.2	Q6IMN6-10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.58	T
PhyloP100		1.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.065
Sift	Benign	0.087	T
Sift4G	Benign	0.083	T
Polyphen		0.41	B
Vest4		0.079
MVP		0.57
MPC		0.11
ClinPred		0.20	T
GERP RS		3.8
gMVP		0.31
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs150951809; hg19: chr12-30863255;