Genetic Variant CAPRIN2:p.Tyr806Tyr (chr12-30713872-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001385503.1(CAPRIN2):c.2418T>C(p.Tyr806Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,593,526 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 33 hom. )

Consequence

CAPRIN2
NM_001385503.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0660

Variant links:

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]

CAPRIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 12-30713872-A-G is Benign according to our data. Variant chr12-30713872-A-G is described in ClinVar as [Benign]. Clinvar id is 786224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00808 (1231/152316) while in subpopulation AFR AF= 0.0275 (1143/41574). AF 95% confidence interval is 0.0262. There are 18 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPRIN2	NM_001385503.1 link	c.2418T>C	p.Tyr806Tyr	synonymous_variant	Exon 17 of 19	ENST00000695402.1	NP_001372432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN2	ENST00000695402.1 link	c.2418T>C	p.Tyr806Tyr	synonymous_variant	Exon 17 of 19		NM_001385503.1	ENSP00000511883.1		F5H5J8

Frequencies

GnomAD3 genomes

AF:

0.00808

AC:

1230

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00217

AC:

543

AN:

249774

Hom.:

AF XY:

0.00168

AC XY:

227

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.000755

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00196

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.00127

AC:

1829

AN:

1441210

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

829

AN XY:

718142

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.0000467

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000850

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00808

AC:

1231

AN:

152316

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00522

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00859

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.0

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over