3-46979842-G-GGCCGGA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_015175.3(NBEAL2):​c.-14_-9dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 441,060 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

NBEAL2
NM_015175.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
Variant links:
Genes affected
NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]
CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00109 (165/151852) while in subpopulation AMR AF= 0.0036 (55/15262). AF 95% confidence interval is 0.00284. There are 1 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBEAL2NM_015175.3 linkuse as main transcriptc.-14_-9dup 5_prime_UTR_variant 1/54 ENST00000450053.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBEAL2ENST00000450053.8 linkuse as main transcriptc.-14_-9dup 5_prime_UTR_variant 1/542 NM_015175.3 P2Q6ZNJ1-1

Frequencies

GnomAD3 genomes
AF:
0.00109
AC:
165
AN:
151744
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00361
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.0000956
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00109
Gnomad OTH
AF:
0.000481
GnomAD3 exomes
AF:
0.000565
AC:
12
AN:
21252
Hom.:
0
AF XY:
0.000831
AC XY:
11
AN XY:
13244
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00154
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000259
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00120
AC:
347
AN:
289208
Hom.:
1
Cov.:
0
AF XY:
0.00125
AC XY:
197
AN XY:
158018
show subpopulations
Gnomad4 AFR exome
AF:
0.000142
Gnomad4 AMR exome
AF:
0.00225
Gnomad4 ASJ exome
AF:
0.00343
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00390
Gnomad4 FIN exome
AF:
0.000570
Gnomad4 NFE exome
AF:
0.000986
Gnomad4 OTH exome
AF:
0.00182
GnomAD4 genome
AF:
0.00109
AC:
165
AN:
151852
Hom.:
1
Cov.:
33
AF XY:
0.00104
AC XY:
77
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00311
Gnomad4 FIN
AF:
0.0000956
Gnomad4 NFE
AF:
0.00109
Gnomad4 OTH
AF:
0.000476
Alfa
AF:
0.00135
Hom.:
0
Bravo
AF:
0.00133
Asia WGS
AF:
0.00117
AC:
4
AN:
3428

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Gray platelet syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs764010884; hg19: chr3-47021332; API