17-81035353-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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

GnomAD2 exomes AF: 0.901 AC: 54029 AN: 59956 AF XY: 0.903

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 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 AC: 16570 AN: 20634

Gnomad4 AMR exome AF: 0.920 AC: 8828 AN: 9594

Gnomad4 ASJ exome AF: 0.885 AC: 12916 AN: 14590

Gnomad4 EAS exome AF: 0.930 AC: 15833 AN: 17032

Gnomad4 SAS exome AF: 0.920 AC: 38588 AN: 41956

Gnomad4 FIN exome AF: 0.902 AC: 28872 AN: 32016

Gnomad4 NFE exome AF: 0.908 AC: 821091 AN: 904680

Gnomad4 Remaining exome AF: 0.905 AC: 36100 AN: 39888

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 AC: 0.817985 AN: 0.817985

Gnomad4 AMR AF: 0.918 AC: 0.918396 AN: 0.918396

Gnomad4 ASJ AF: 0.897 AC: 0.896592 AN: 0.896592

Gnomad4 EAS AF: 0.936 AC: 0.935649 AN: 0.935649

Gnomad4 SAS AF: 0.936 AC: 0.935738 AN: 0.935738

Gnomad4 FIN AF: 0.904 AC: 0.903875 AN: 0.903875

Gnomad4 NFE AF: 0.905 AC: 0.905091 AN: 0.905091

Gnomad4 OTH AF: 0.875 AC: 0.874758 AN: 0.874758

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
Mutation Taster		=100/0	polymorphism (auto)

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;