rs150797250

chr16-56484848-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_031885.5(BBS2):c.2079G>A(p.Gln693=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,613,970 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (15 hom.)
• Consequence: BBS2 NM_031885.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.243

Genes affected

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 16-56484848-C-T is Benign according to our data. Variant chr16-56484848-C-T is described in ClinVar as [Benign]. Clinvar id is 319849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56484848-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.243 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00065 (99/152298) while in subpopulation EAS AF= 0.016 (83/5180). AF 95% confidence interval is 0.0132. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS2	NM_031885.5	c.2079G>A	p.Gln693=	synonymous_variant	17/17	ENST00000245157.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS2	ENST00000245157.11	c.2079G>A	p.Gln693=	synonymous_variant	17/17	1	NM_031885.5	P1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00156 AC: 392 AN: 251310 Hom.: 6 AF XY: 0.00133 AC XY: 181 AN XY: 135846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.0184

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000885 AC: 1294 AN: 1461672 Hom.: 15 Cov.: 30 AF XY: 0.000842 AC XY: 612 AN XY: 727152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.0271

Gnomad4 SAS exome AF: 0.000893

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000612

Gnomad4 OTH exome AF: 0.000778

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000819 AC XY: 61 AN XY: 74466

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000665

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Bardet-Biedl syndrome 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Dec 03, 2019	- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	4.1
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs150797250; hg19: chr16-56518760;