ENST00000682930.1:c.42+6951C>A

Variant names:

• chr16-56563724-G-T
• rs1566441
• ENST00000682930.1:c.42+6951C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682930.1(BBS2):​c.42+6951C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,032 control chromosomes in the GnomAD database, including 15,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15548 hom., cov: 33)
• Consequence: BBS2 ENST00000682930.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• 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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000682930.1	c.42+6951C>A		intron_variant	Intron 2 of 18			ENSP00000507981.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66206 AN: 151914 Hom.: 15546 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66222 AN: 152032 Hom.: 15548 Cov.: 33 AF XY: 0.430 AC XY: 31984 AN XY: 74304

African (AFR) AF: 0.280 AC: 11589 AN: 41462

American (AMR) AF: 0.443 AC: 6761 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1583 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1037 AN: 5178

South Asian (SAS) AF: 0.438 AC: 2114 AN: 4824

European-Finnish (FIN) AF: 0.496 AC: 5238 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36240 AN: 67958

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.499 Hom.: 34539

Bravo AF: 0.422

Asia WGS AF: 0.325 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.43
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs1566441; hg19: chr16-56597636;