rs4784675

Variant names:

• chr16-56506278-G-C
• rs4784675
• NM_031885.5:c.613-54C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• BBS2-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 74

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031885.5. 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
	BBS2	NM_031885.5	MANE Select	c.613-54C>G		intron	N/A	NP_114091.4
	BBS2	NM_001377456.1		c.613-54C>G		intron	N/A	NP_001364385.1	Q9BXC9
	BBS2	NR_165293.1		n.775-54C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS2	ENST00000245157.11	TSL:1 MANE Select	c.613-54C>G		intron	N/A	ENSP00000245157.5	Q9BXC9
	BBS2	ENST00000565781.6	TSL:1	n.627-54C>G		intron	N/A
	BBS2	ENST00000682188.1		c.613-54C>G		intron	N/A	ENSP00000507655.1	A0A804HJV0

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

African (AFR) AF: 0.214 AC: 5977 AN: 27958

American (AMR) AF: 0.126 AC: 5485 AN: 43560

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 1779 AN: 24542

East Asian (EAS) AF: 0.200 AC: 7480 AN: 37470

South Asian (SAS) AF: 0.211 AC: 16857 AN: 80036

European-Finnish (FIN) AF: 0.136 AC: 6750 AN: 49510

Middle Eastern (MID) AF: 0.154 AC: 809 AN: 5256

European-Non Finnish (NFE) AF: 0.150 AC: 131852 AN: 880304

Other (OTH) AF: 0.156 AC: 8084 AN: 51730

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

African (AFR) AF: 0.207 AC: 8601 AN: 41456

American (AMR) AF: 0.124 AC: 1895 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1161 AN: 5174

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1464 AN: 10582

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10048 AN: 67974

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.155 Hom.: 236

Bravo AF: 0.164

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome 2 (1)
-	-	1	Retinitis pigmentosa 74 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.50
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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