rs1436442266

Variant names:

• chr12-51292271-T-G
• rs1436442266
• NM_016293.4:c.835A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-51292271-T-G
• chr12-51292271-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016293.4(BIN2):​c.835A>C​(p.Thr279Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,449,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: BIN2 NM_016293.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3128366).

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.835A>C	p.Thr279Pro	missense	Exon 10 of 13	NP_057377.4
	BIN2	NM_001364779.1		c.832A>C	p.Thr278Pro	missense	Exon 10 of 13	NP_001351708.1
	BIN2	NM_001290007.2		c.757A>C	p.Thr253Pro	missense	Exon 10 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.835A>C	p.Thr279Pro	missense	Exon 10 of 13	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.1457A>C		non_coding_transcript_exon	Exon 9 of 12
	BIN2	ENST00000871152.1		c.832A>C	p.Thr278Pro	missense	Exon 10 of 13	ENSP00000541211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241372 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000690 AC: 10 AN: 1449696 Hom.: 0 Cov.: 36 AF XY: 0.00000416 AC XY: 3 AN XY: 721618

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

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	0.075
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.68	D
PhyloP100		3.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.28	T
Vest4		0.22
MVP		0.82
ClinPred		0.65	D
GERP RS		5.2
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1436442266; hg19: chr12-51686055;