chr12-51292007-T-C

Variant names:

• chr12-51292007-T-C
• rs757294613
• NM_016293.4:c.1099A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016293.4(BIN2):​c.1099A>G​(p.Thr367Ala) 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. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIN2 NM_016293.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038475394).
• BP6: Variant 12-51292007-T-C is Benign according to our data. Variant chr12-51292007-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3260935.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1099A>G	p.Thr367Ala	missense	Exon 10 of 13	NP_057377.4
	BIN2	NM_001364779.1		c.1096A>G	p.Thr366Ala	missense	Exon 10 of 13	NP_001351708.1
	BIN2	NM_001290007.2		c.1021A>G	p.Thr341Ala	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.1099A>G	p.Thr367Ala	missense	Exon 10 of 13	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.1721A>G		non_coding_transcript_exon	Exon 9 of 12
	BIN2	ENST00000871152.1		c.1096A>G	p.Thr366Ala	missense	Exon 10 of 13	ENSP00000541211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251408 AF XY: 0.00000736

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.054
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.66
DANN	Benign	0.34
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.038	T
MetaSVM	Uncertain	-0.28	T
PhyloP100		-0.33
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	0.95	T
Vest4		0.020
MVP		0.36
ClinPred		0.040	T
GERP RS		-3.3
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757294613; hg19: chr12-51685791;