Genetic Variant NM_001144888.2:c.490-1717A>G (chr17-81098211-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001144888.2(BAIAP2):c.490-1717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,357,926 control chromosomes in the GnomAD database, including 42,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.21 ( 4027 hom., cov: 32)

Exomes 𝑓: 0.25 ( 38407 hom. )

Consequence

BAIAP2
NM_001144888.2 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.325

Variant links:

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]

BAIAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2	NM_001144888.2 link	c.490-1717A>G		intron_variant	Intron 6 of 13	ENST00000428708.7	NP_001138360.1	Q9UQB8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP2	ENST00000428708.7 link	c.490-1717A>G		intron_variant	Intron 6 of 13	1	NM_001144888.2	ENSP00000401022.2		Q9UQB8-2

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32421

AN:

151986

Hom.:

4030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.252

AC:

13281

AN:

52750

Hom.:

1790

AF XY:

0.247

AC XY:

7414

AN XY:

29992

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.531

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.250

AC:

301961

AN:

1205820

Hom.:

38407

Cov.:

AF XY:

0.250

AC XY:

146739

AN XY:

586278

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.213

AC:

32430

AN:

152106

Hom.:

4027

Cov.:

AF XY:

0.209

AC XY:

15563

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.487

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.231

Hom.:

1194

Bravo

AF:

0.216

Asia WGS

AF:

0.357

AC:

1237

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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 rs72634327 with Attention-deficit hyperactivity disorder. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.66

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over