12-51291644-G-T

Variant names:

• chr12-51291644-G-T
• rs769469897
• NM_016293.4:c.1462C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016293.4(BIN2):​c.1462C>A​(p.His488Asn) 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. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIN2 NM_016293.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053185076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN2	NM_016293.4	c.1462C>A	p.His488Asn	missense_variant	Exon 10 of 13	ENST00000615107.6	NP_057377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN2	ENST00000615107.6	c.1462C>A	p.His488Asn	missense_variant	Exon 10 of 13	1	NM_016293.4	ENSP00000483983.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.043
DANN	Benign	0.21
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Uncertain	0.0058	D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.020	.;N
REVEL	Benign	0.14
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Vest4		0.085
MVP		0.34
ClinPred		0.038	T
GERP RS		-3.0

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: rs769469897; hg19: chr12-51685428;