17-81035353-T-C

Variant names:

• chr17-81035353-T-C
• rs8073224
• NM_001144888.2:c.54+45T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144888.2(BAIAP2):​c.54+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,231,708 control chromosomes in the GnomAD database, including 502,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.88 (57981 hom., cov: 31)
  • Exomes 𝑓: 0.91 (444929 hom.)
• Consequence: BAIAP2 NM_001144888.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.53

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2	NM_001144888.2	c.54+45T>C		intron_variant	Intron 1 of 13	ENST00000428708.7	NP_001138360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP2	ENST00000428708.7	c.54+45T>C		intron_variant	Intron 1 of 13	1	NM_001144888.2	ENSP00000401022.2

Frequencies

GnomAD3 genomes AF: 0.884 AC: 130896 AN: 148152 Hom.: 57949 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.913

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.873

GnomAD3 exomes AF: 0.901 AC: 54029 AN: 59956 Hom.: 24368 AF XY: 0.903 AC XY: 32057 AN XY: 35488

Gnomad AFR exome AF: 0.771

Gnomad AMR exome AF: 0.921

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.874

Gnomad SAS exome AF: 0.919

Gnomad FIN exome AF: 0.906

Gnomad NFE exome AF: 0.897

Gnomad OTH exome AF: 0.906

GnomAD4 exome AF: 0.906 AC: 981505 AN: 1083448 Hom.: 444929 Cov.: 21 AF XY: 0.906 AC XY: 479152 AN XY: 528830

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.920

Gnomad4 ASJ exome AF: 0.885

Gnomad4 EAS exome AF: 0.930

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.905

GnomAD4 genome AF: 0.883 AC: 130977 AN: 148260 Hom.: 57981 Cov.: 31 AF XY: 0.885 AC XY: 63984 AN XY: 72262

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.936

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.875

Alfa AF: 0.893 Hom.: 7554

Bravo AF: 0.883

Asia WGS AF: 0.927 AC: 3054 AN: 3296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Attention deficit hyperactivity disorder Uncertain:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gene Variants in BAIAP2 have been studied in several populations and are known to cause ADHD. Potent variants of this gene prevent neuronal growth, maturation and survival, essential for proper functioning of frontal cortical and subcortical circuits. However, more clinical evidence is required to confer the association of this particular variant rs8073224 with Attention-deficit hyperactivity disorder. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.5
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs8073224; hg19: chr17-79009153;