rs191207351

chr16-56509915-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031885.5(BBS2):c.612+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 1,595,852 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0098 (91 hom.)
• Consequence: BBS2 NM_031885.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-56509915-A-G is Benign according to our data. Variant chr16-56509915-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00693 (1054/152178) while in subpopulation NFE AF= 0.0116 (789/67998). AF 95% confidence interval is 0.0109. There are 8 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS2	NM_031885.5	c.612+42T>C		intron_variant		ENST00000245157.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS2	ENST00000245157.11	c.612+42T>C		intron_variant		1	NM_031885.5	P1

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1054 AN: 152060 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00698 AC: 1755 AN: 251296 Hom.: 10 AF XY: 0.00713 AC XY: 969 AN XY: 135838

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00803

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00981 AC: 14168 AN: 1443674 Hom.: 91 Cov.: 26 AF XY: 0.00973 AC XY: 7001 AN XY: 719398

Gnomad4 AFR exome AF: 0.00172

Gnomad4 AMR exome AF: 0.00403

Gnomad4 ASJ exome AF: 0.00542

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.00708

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.00737

GnomAD4 genome AF: 0.00693 AC: 1054 AN: 152178 Hom.: 8 Cov.: 32 AF XY: 0.00665 AC XY: 495 AN XY: 74384

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00944

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.0103 Hom.: 1

Bravo AF: 0.00674

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.16
Dann	Benign	0.57

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: rs191207351; hg19: chr16-56543827; COSMIC: COSV104392617; COSMIC: COSV104392617;