17-81099973-G-C

Variant names:

• chr17-81099973-G-C
• rs372635764
• NM_001144888.2:c.535G>C

Variant summary

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

The NM_001385157.1(BAIAP2):​c.-195G>C variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BAIAP2 NM_001385157.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 3 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_001385157.1. 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.535G>C	p.Val179Leu	missense	Exon 7 of 14	NP_001138360.1	Q9UQB8-2
	BAIAP2	NM_001385157.1		c.-195G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001372086.1
	BAIAP2	NM_001385158.1		c.-195G>C		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	NP_001372087.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAIAP2	ENST00000428708.7	TSL:1 MANE Select	c.535G>C	p.Val179Leu	missense	Exon 7 of 14	ENSP00000401022.2	Q9UQB8-2
	BAIAP2	ENST00000321300.10	TSL:1	c.535G>C	p.Val179Leu	missense	Exon 7 of 15	ENSP00000316338.6	Q9UQB8-1
	BAIAP2	ENST00000321280.11	TSL:1	c.535G>C	p.Val179Leu	missense	Exon 7 of 14	ENSP00000315685.7	Q9UQB8-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.010
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.060	T
Sift4G	Benign	0.26	T
Polyphen		0.49	P
Vest4		0.65
MutPred		0.64		Loss of methylation at K184 (P = 0.0886)
MVP		0.82
MPC		0.90
ClinPred		0.88	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.50

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: rs372635764; hg19: chr17-79073773;