17-81035301-T-A

Variant names:

• chr17-81035301-T-A
• NM_001144888.2:c.47T>A

Variant summary

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

The NM_001144888.2(BAIAP2):​c.47T>A​(p.Val16Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAIAP2 NM_001144888.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946
• Publications: 0 publications found

Genes affected

BAIAP2 (HGNC:947): (BAR/IMD domain containing adaptor protein 2) The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein. This adaptor protein links membrane bound G-proteins to cytoplasmic effector proteins. This protein functions as an insulin receptor tyrosine kinase substrate and suggests a role for insulin in the central nervous system. It also associates with a downstream effector of Rho small G proteins, which is associated with the formation of stress fibers and cytokinesis. This protein is involved in lamellipodia and filopodia formation in motile cells and may affect neuronal growth-cone guidance. This protein has also been identified as interacting with the dentatorubral-pallidoluysian atrophy gene, which is associated with an autosomal dominant neurodegenerative disease. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144888.2. 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
	BAIAP2	NM_001144888.2	MANE Select	c.47T>A	p.Val16Asp	missense	Exon 1 of 14	NP_001138360.1	Q9UQB8-2
	BAIAP2	NM_001385129.1		c.47T>A	p.Val16Asp	missense	Exon 1 of 17	NP_001372058.1
	BAIAP2	NM_001385130.1		c.47T>A	p.Val16Asp	missense	Exon 1 of 15	NP_001372059.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAIAP2	ENST00000428708.7	TSL:1 MANE Select	c.47T>A	p.Val16Asp	missense	Exon 1 of 14	ENSP00000401022.2	Q9UQB8-2
	BAIAP2	ENST00000321300.10	TSL:1	c.47T>A	p.Val16Asp	missense	Exon 1 of 15	ENSP00000316338.6	Q9UQB8-1
	BAIAP2	ENST00000321280.11	TSL:1	c.47T>A	p.Val16Asp	missense	Exon 1 of 14	ENSP00000315685.7	Q9UQB8-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.68	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.95
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.62		Gain of disorder (P = 0.0068)
MVP		0.82
MPC		2.1
ClinPred		0.93	D
GERP RS		2.2
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.94
Mutation Taster		=57/43	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

Other links and lift over

hg19: chr17-79009101;