12-51297150-T-G

Variant names:

• chr12-51297150-T-G
• NM_016293.4:c.617A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016293.4(BIN2):​c.617A>C​(p.Tyr206Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BIN2 NM_016293.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

Genes affected

BIN2 (HGNC:1053): (bridging integrator 2) Enables phospholipid binding activity. Involved in several processes, including phagocytosis, engulfment; plasma membrane tubulation; and podosome assembly. Located in plasma membrane and podosome. Colocalizes with phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN2	NM_016293.4	c.617A>C	p.Tyr206Ser	missense_variant	Exon 8 of 13	ENST00000615107.6	NP_057377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN2	ENST00000615107.6	c.617A>C	p.Tyr206Ser	missense_variant	Exon 8 of 13	1	NM_016293.4	ENSP00000483983.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461638 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.011	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.8	.;D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.94
MVP		0.91
ClinPred		1.0	D
GERP RS		4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-51690934;