rs1018314879

Variant names:

• chr16-56501455-C-G
• rs1018314879
• NM_031885.5:c.1123G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56501455-C-G
• chr16-56501455-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031885.5(BBS2):​c.1123G>C​(p.Gly375Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G375S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BBS2 NM_031885.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 7.31
• Publications: 0 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

ENSG00000288725 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

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.1123G>C	p.Gly375Arg	missense	Exon 10 of 17	NP_114091.4
	BBS2	NM_001377456.1		c.1123G>C	p.Gly375Arg	missense	Exon 10 of 18	NP_001364385.1
	BBS2	NR_165293.1		n.1285G>C		non_coding_transcript_exon	Exon 10 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS2	ENST00000245157.11	TSL:1 MANE Select	c.1123G>C	p.Gly375Arg	missense	Exon 10 of 17	ENSP00000245157.5
	BBS2	ENST00000565781.6	TSL:1	n.2172G>C		non_coding_transcript_exon	Exon 8 of 12
	ENSG00000288725	ENST00000684388.1		n.43G>C		non_coding_transcript_exon	Exon 1 of 14	ENSP00000507647.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bardet-Biedl syndrome 2;C4225281:Retinitis pigmentosa 74 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Pathogenic	0.87	D
PhyloP100		7.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Vest4		0.78
MutPred		0.56		Gain of solvent accessibility (P = 0.0171)
MVP		0.93
MPC		0.96
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.72
Mutation Taster		=8/92	disease causing

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: rs1018314879; hg19: chr16-56535367;