17-81103931-C-A

Variant names:

• chr17-81103931-C-A
• rs776209043
• NM_001144888.2:c.889C>A

Variant summary

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

The NM_001144888.2(BAIAP2):​c.889C>A​(p.Pro297Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: BAIAP2 NM_001144888.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2175439).

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.889C>A	p.Pro297Thr	missense	Exon 9 of 14	NP_001138360.1	Q9UQB8-2
	BAIAP2	NM_001385129.1		c.988C>A	p.Pro330Thr	missense	Exon 10 of 17	NP_001372058.1
	BAIAP2	NM_001385130.1		c.988C>A	p.Pro330Thr	missense	Exon 10 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.889C>A	p.Pro297Thr	missense	Exon 9 of 14	ENSP00000401022.2	Q9UQB8-2
	BAIAP2	ENST00000321300.10	TSL:1	c.889C>A	p.Pro297Thr	missense	Exon 9 of 15	ENSP00000316338.6	Q9UQB8-1
	BAIAP2	ENST00000321280.11	TSL:1	c.889C>A	p.Pro297Thr	missense	Exon 9 of 14	ENSP00000315685.7	Q9UQB8-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250622 AF XY: 0.0000589

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460678 Hom.: 0 Cov.: 34 AF XY: 0.0000303 AC XY: 22 AN XY: 726642

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52242

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000494 AC: 6

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	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.0019
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.055	T
Polyphen		0.98	D
Vest4		0.38
MutPred		0.20		Gain of glycosylation at P297 (P = 0.046)
MVP		0.95
MPC		0.83
ClinPred		0.24	T
GERP RS		4.2
PromoterAI		-0.0072	Neutral
Varity_R		0.33
gMVP		0.66
Mutation Taster		=63/37	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

dbSNP: rs776209043; hg19: chr17-79077731;