17-81103971-A-G

Variant names:

• chr17-81103971-A-G
• NM_001144888.2:c.929A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144888.2(BAIAP2):​c.929A>G​(p.Tyr310Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BAIAP2 NM_001144888.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2	NM_001144888.2	c.929A>G	p.Tyr310Cys	missense_variant	Exon 9 of 14	ENST00000428708.7	NP_001138360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP2	ENST00000428708.7	c.929A>G	p.Tyr310Cys	missense_variant	Exon 9 of 14	1	NM_001144888.2	ENSP00000401022.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460764 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.929A>G (p.Y310C) alteration is located in exon 9 (coding exon 9) of the BAIAP2 gene. This alteration results from a A to G substitution at nucleotide position 929, causing the tyrosine (Y) at amino acid position 310 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	.;.;.;.;.;D;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.0	M;M;M;.;M;M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D;D;.;.;D;D;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D;D;.;.;D;D;.;D
Sift4G	Uncertain	0.010	D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;D;D;.;D
Vest4		0.90
MutPred		0.24		Loss of phosphorylation at Y310 (P = 0.0096);Loss of phosphorylation at Y310 (P = 0.0096);Loss of phosphorylation at Y310 (P = 0.0096);.;Loss of phosphorylation at Y310 (P = 0.0096);Loss of phosphorylation at Y310 (P = 0.0096);.;.;
MVP		0.89
MPC		2.0
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.81

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79077771;