chr12-51297150-T-G

Variant names:

• chr12-51297150-T-G
• rs927716722
• NM_016293.4:c.617A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y206C) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

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, 0.912

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016293.4. 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
	BIN2	NM_016293.4	MANE Select	c.617A>C	p.Tyr206Ser	missense	Exon 8 of 13	NP_057377.4
	BIN2	NM_001364779.1		c.617A>C	p.Tyr206Ser	missense	Exon 8 of 13	NP_001351708.1
	BIN2	NM_001290007.2		c.539A>C	p.Tyr180Ser	missense	Exon 8 of 13	NP_001276936.1	Q9UBW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN2	ENST00000615107.6	TSL:1 MANE Select	c.617A>C	p.Tyr206Ser	missense	Exon 8 of 13	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.1239A>C		non_coding_transcript_exon	Exon 7 of 12
	BIN2	ENST00000871152.1		c.617A>C	p.Tyr206Ser	missense	Exon 8 of 13	ENSP00000541211.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.011	D
PhyloP100		6.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.94
MVP		0.91
ClinPred		1.0	D
GERP RS		4.8
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs927716722; hg19: chr12-51690934;