12-30711571-G-C

Variant names:

• chr12-30711571-G-C
• rs150085536
• NM_001385503.1:c.2564C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385503.1(CAPRIN2):​c.2564C>G​(p.Ser855Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S855L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAPRIN2 NM_001385503.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 7 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2702537).

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.2564C>G	p.Ser855Trp	missense	Exon 18 of 19	NP_001372432.1	F5H5J8
	CAPRIN2	NM_001002259.3		c.2810C>G	p.Ser937Trp	missense	Exon 17 of 18	NP_001002259.1	Q6IMN6-1
	CAPRIN2	NM_001319843.2		c.2807C>G	p.Ser936Trp	missense	Exon 17 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.2564C>G	p.Ser855Trp	missense	Exon 18 of 19	ENSP00000511883.1	F5H5J8
	CAPRIN2	ENST00000298892.9	TSL:1	c.2660C>G	p.Ser887Trp	missense	Exon 16 of 17	ENSP00000298892.5	Q6IMN6-2
	CAPRIN2	ENST00000417045.5	TSL:1	c.2807C>G	p.Ser936Trp	missense	Exon 17 of 18	ENSP00000391479.1	Q6IMN6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460520 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110808

Other (OTH) AF: 0.00 AC: 0 AN: 60348

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.028	D
PhyloP100		6.1
PROVEAN	Benign	0.74	N
REVEL	Benign	0.091
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.044	D
MutPred		0.31		Gain of catalytic residue at E694 (P = 4e-04)
MVP		0.40
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=68/32	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: rs150085536; hg19: chr12-30864505;