12-51281503-A-G

Variant names:

• chr12-51281503-A-G
• rs1945119299
• NM_016293.4:c.1694T>C

Variant summary

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

The NM_016293.4(BIN2):​c.1694T>C​(p.Leu565Pro) 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIN2 NM_016293.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.919
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0818041).

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.1694T>C	p.Leu565Pro	missense	Exon 13 of 13	NP_057377.4
	BIN2	NM_001364779.1		c.1691T>C	p.Leu564Pro	missense	Exon 13 of 13	NP_001351708.1
	BIN2	NM_001290007.2		c.1616T>C	p.Leu539Pro	missense	Exon 13 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.1694T>C	p.Leu565Pro	missense	Exon 13 of 13	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.2316T>C		non_coding_transcript_exon	Exon 12 of 12
	BIN2	ENST00000871152.1		c.1691T>C	p.Leu564Pro	missense	Exon 13 of 13	ENSP00000541211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
PhyloP100		0.92
Mutation Taster		=88/12	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1945119299; hg19: chr12-51675287;