Genetic Variant BIN2:p.Glu517Lys (chr12-51288155-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016293.4(BIN2):c.1549G>A(p.Glu517Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

BIN2
NM_016293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Publications

4 publications found

Variant links:

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]

BIN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07155934).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN2	NM_016293.4	MANE Select	c.1549G>A	p.Glu517Lys	missense	Exon 11 of 13	NP_057377.4
BIN2	NM_001364779.1		c.1546G>A	p.Glu516Lys	missense	Exon 11 of 13	NP_001351708.1
BIN2	NM_001290007.2		c.1471G>A	p.Glu491Lys	missense	Exon 11 of 13	NP_001276936.1	Q9UBW5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN2	ENST00000615107.6	TSL:1 MANE Select	c.1549G>A	p.Glu517Lys	missense	Exon 11 of 13	ENSP00000483983.2	Q9UBW5-1
BIN2	ENST00000605039.5	TSL:1	n.2171G>A		non_coding_transcript_exon	Exon 10 of 12
BIN2	ENST00000871152.1		c.1546G>A	p.Glu516Lys	missense	Exon 11 of 13	ENSP00000541211.1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000235

AC:

AN:

251450

AF XY:

0.000250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

290

AN:

1461644

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

160

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.000393

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000237

AC:

264

AN:

1111808

Other (OTH)

AF:

0.0000497

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000321

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.85

M_CAP

Benign

0.076

MetaRNN

Benign

0.072

MetaSVM

Uncertain

0.19

PhyloP100

1.2

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.16

REVEL

Benign

0.19

Sift

Benign

0.086

Sift4G

Uncertain

0.055

Vest4

0.32

MVP

0.60

ClinPred

0.044

GERP RS

3.0

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over