chr9-16419273-C-T

Variant names:

• chr9-16419273-C-T
• rs1199209096
• NM_017637.6:c.3016G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017637.6(BNC2):​c.3016G>A​(p.Ala1006Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. A1006V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BNC2 NM_017637.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 1 publications found

Genes affected

BNC2 (HGNC:30988): (basonuclin zinc finger protein 2) This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]

BNC2 Gene-Disease associations (from GenCC):

• lower urinary tract obstruction, congenital

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• posterior urethral valve

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0772059).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017637.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	NM_017637.6	MANE Select	c.3016G>A	p.Ala1006Thr	missense	Exon 7 of 7	NP_060107.3
	BNC2	NM_001317940.2		c.2731G>A	p.Ala911Thr	missense	Exon 6 of 6	NP_001304869.1
	BNC2	NM_001317939.2		c.*360G>A		3_prime_UTR	Exon 7 of 7	NP_001304868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	ENST00000380672.9	TSL:2 MANE Select	c.3016G>A	p.Ala1006Thr	missense	Exon 7 of 7	ENSP00000370047.3	Q6ZN30-1
	BNC2	ENST00000545497.5	TSL:1	c.*360G>A		3_prime_UTR	Exon 7 of 7	ENSP00000444640.2	F5H586
	BNC2	ENST00000411752.5	TSL:1	c.*392G>A		3_prime_UTR	Exon 5 of 5	ENSP00000392212.1	H0Y4J1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
PhyloP100		2.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.030
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.020
MutPred		0.34		Gain of phosphorylation at A1006 (P = 0.005)
MVP		0.093
MPC		0.13
ClinPred		0.41	T
GERP RS		5.2
Varity_R		0.080
gMVP		0.29
Mutation Taster		=87/13	polymorphism

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: rs1199209096; hg19: chr9-16419271; COSMIC: COSV108235386;