NM_031885.5:c.612+311T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS2	NM_031885.5	MANE Select	c.612+311T>C		intron	N/A	NP_114091.4
	BBS2	NM_001377456.1		c.612+311T>C		intron	N/A	NP_001364385.1
	BBS2	NR_165293.1		n.774+311T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS2	ENST00000245157.11	TSL:1 MANE Select	c.612+311T>C		intron	N/A	ENSP00000245157.5
	BBS2	ENST00000565781.6	TSL:1	n.626+311T>C		intron	N/A
	BBS2	ENST00000565859.2	TSL:3	n.578T>C		non_coding_transcript_exon	Exon 3 of 14

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

African (AFR) AF: 0.930 AC: 5880 AN: 6324

American (AMR) AF: 0.617 AC: 5696 AN: 9234

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 3082 AN: 5162

East Asian (EAS) AF: 0.607 AC: 6254 AN: 10298

South Asian (SAS) AF: 0.737 AC: 20079 AN: 27238

European-Finnish (FIN) AF: 0.489 AC: 3858 AN: 7892

Middle Eastern (MID) AF: 0.629 AC: 443 AN: 704

European-Non Finnish (NFE) AF: 0.615 AC: 67420 AN: 109706

Other (OTH) AF: 0.628 AC: 6396 AN: 10178

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

African (AFR) AF: 0.925 AC: 38442 AN: 41570

American (AMR) AF: 0.614 AC: 9389 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2026 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3092 AN: 5178

South Asian (SAS) AF: 0.740 AC: 3570 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 5014 AN: 10578

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41861 AN: 67970

Other (OTH) AF: 0.662 AC: 1399 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.66
PhyloP100		-0.21
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: rs9937444; hg19: chr16-56543558;