9-16419500-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017637.6(BNC2):c.2789A>G(p.Asp930Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0033 in 1,614,038 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D930N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0034 (12 hom.)
• Consequence: BNC2 NM_017637.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 4.05

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00668028).
• BP6: Variant 9-16419500-T-C is Benign according to our data. Variant chr9-16419500-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 120239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 395 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNC2	NM_017637.6	c.2789A>G	p.Asp930Gly	missense_variant	7/7	ENST00000380672.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNC2	ENST00000380672.9	c.2789A>G	p.Asp930Gly	missense_variant	7/7	2	NM_017637.6	P2

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 395 AN: 152044 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00421

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00267 AC: 671 AN: 250904 Hom.: 3 AF XY: 0.00250 AC XY: 339 AN XY: 135640

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00489

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00338 AC: 4938 AN: 1461874 Hom.: 12 Cov.: 35 AF XY: 0.00328 AC XY: 2382 AN XY: 727238

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00273

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.00260 AC: 395 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.00241 AC XY: 179 AN XY: 74396

Gnomad4 AFR AF: 0.000987

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00421

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00368 Hom.: 2

Bravo AF: 0.00230

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00360 AC: 31

ExAC AF: 0.00274 AC: 333

EpiCase AF: 0.00316

EpiControl AF: 0.00320

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	BNC2: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 30, 2023	- -

BNC2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 10, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypotension Other:1

not provided, no classification provided

literature only

Centre for molecular medicine, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.092	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.20
Sift	Benign	0.049	D;T
Sift4G	Benign	0.20	T;T
Polyphen		0.99	D;.
Vest4		0.12
MVP		0.21
MPC		0.17
ClinPred		0.023	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.59

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: rs41268965; hg19: chr9-16419498;