rs4784675

Positions:

• chr16-56506278-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031885.5(BBS2):​c.613-54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,352,452 control chromosomes in the GnomAD database, including 17,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2232 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15128 hom.)
• Consequence: BBS2 NM_031885.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.122

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]

BBS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-56506278-G-C is Benign according to our data. Variant chr16-56506278-G-C is described in ClinVar as [Benign]. Clinvar id is 1172737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS2	NM_031885.5	c.613-54C>G		intron_variant		ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11	c.613-54C>G		intron_variant		1	NM_031885.5	ENSP00000245157.5

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24911 AN: 151968 Hom.: 2229 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.154 AC: 185073 AN: 1200366 Hom.: 15128 AF XY: 0.156 AC XY: 95098 AN XY: 609318

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0725

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.164 AC: 24939 AN: 152086 Hom.: 2232 Cov.: 32 AF XY: 0.163 AC XY: 12113 AN XY: 74362

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.164

Alfa AF: 0.155 Hom.: 236

Bravo AF: 0.164

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 74 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Bardet-Biedl syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.50

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: rs4784675; hg19: chr16-56540190; COSMIC: COSV104392583; COSMIC: COSV104392583;