NM_031885.5:c.1380C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_031885.5(BBS2):c.1380C>T(p.Phe460Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00092 ( 0 hom. )

Consequence

BBS2
NM_031885.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 1.16

Publications

3 publications found

Variant links:

COSMIC-nc: COSV104392657

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

BBS2 links:

ENSG00000288725 (HGNC:):

ENSG00000288725 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 16-56500871-G-A is Benign according to our data. Variant chr16-56500871-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 283882.

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BBS2	NM_031885.5	MANE Select	c.1380C>T	p.Phe460Phe	synonymous	Exon 11 of 17	NP_114091.4
BBS2	NM_001377456.1		c.1380C>T	p.Phe460Phe	synonymous	Exon 11 of 18	NP_001364385.1
BBS2	NR_165293.1		n.1542C>T		non_coding_transcript_exon	Exon 11 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BBS2	ENST00000245157.11	TSL:1 MANE Select	c.1380C>T	p.Phe460Phe	synonymous	Exon 11 of 17	ENSP00000245157.5
BBS2	ENST00000565781.6	TSL:1	n.2756C>T		non_coding_transcript_exon	Exon 8 of 12
ENSG00000288725	ENST00000684388.1		n.300C>T		non_coding_transcript_exon	Exon 2 of 14	ENSP00000507647.1

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000875

AC:

220

AN:

251454

AF XY:

0.000868

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000917

AC:

1340

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000881

AC XY:

641

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33476

American (AMR)

AF:

0.000157

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000431

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00111

AC:

1230

AN:

1111994

Other (OTH)

AF:

0.000861

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152196

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41540

American (AMR)

AF:

0.000327

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00149

AC:

101

AN:

67994

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000654

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 2 (2)

not provided (2)

Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

3.2

(source)

DANN

Benign

0.59

PhyloP100

1.2

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over