16-56509646-A-G

Variant names:

• chr16-56509646-A-G
• rs9937444
• NM_031885.5:c.612+311T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031885.5(BBS2):​c.612+311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 338,934 control chromosomes in the GnomAD database, including 77,311 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 0.69 (38346 hom., cov: 32)
  • Exomes 𝑓: 0.64 (38965 hom.)
• Consequence: BBS2 NM_031885.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS2	NM_031885.5	c.612+311T>C		intron_variant	Intron 5 of 16	ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11	c.612+311T>C		intron_variant	Intron 5 of 16	1	NM_031885.5	ENSP00000245157.5

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105380 AN: 152080 Hom.: 38285 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.638 AC: 119108 AN: 186736 Hom.: 38965 Cov.: 0 AF XY: 0.645 AC XY: 64040 AN XY: 99214

Gnomad4 AFR exome AF: 0.930

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.597

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.693 AC: 105490 AN: 152198 Hom.: 38346 Cov.: 32 AF XY: 0.685 AC XY: 50986 AN XY: 74390

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.662

Alfa AF: 0.661 Hom.: 5795

Bravo AF: 0.712

Asia WGS AF: 0.716 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.66

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: rs9937444; hg19: chr16-56543558;