17-81099993-C-T

Variant names:

• chr17-81099993-C-T
• rs146015006
• NM_001144888.2:c.555C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001385157.1(BAIAP2):​c.-175C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,613,386 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (69 hom.)
• Consequence: BAIAP2 NM_001385157.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.69
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-81099993-C-T is Benign according to our data. Variant chr17-81099993-C-T is described in ClinVar as Benign. ClinVar VariationId is 778754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00344 (524/152320) while in subpopulation SAS AF = 0.0391 (189/4828). AF 95% confidence interval is 0.0346. There are 8 homozygotes in GnomAd4. There are 283 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

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.555C>T	p.Thr185Thr	synonymous	Exon 7 of 14	NP_001138360.1	Q9UQB8-2
	BAIAP2	NM_001385157.1		c.-175C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001372086.1
	BAIAP2	NM_001385158.1		c.-175C>T		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.555C>T	p.Thr185Thr	synonymous	Exon 7 of 14	ENSP00000401022.2	Q9UQB8-2
	BAIAP2	ENST00000321300.10	TSL:1	c.555C>T	p.Thr185Thr	synonymous	Exon 7 of 15	ENSP00000316338.6	Q9UQB8-1
	BAIAP2	ENST00000321280.11	TSL:1	c.555C>T	p.Thr185Thr	synonymous	Exon 7 of 14	ENSP00000315685.7	Q9UQB8-4

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 524 AN: 152202 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0389

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00682 AC: 1712 AN: 250862 AF XY: 0.00811

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00914

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00382

Gnomad OTH exome AF: 0.00784

GnomAD4 exome AF: 0.00443 AC: 6466 AN: 1461066 Hom.: 69 Cov.: 31 AF XY: 0.00536 AC XY: 3894 AN XY: 726830

African (AFR) AF: 0.000448 AC: 15 AN: 33478

American (AMR) AF: 0.00255 AC: 114 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0105 AC: 274 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0320 AC: 2757 AN: 86242

European-Finnish (FIN) AF: 0.00163 AC: 86 AN: 52728

Middle Eastern (MID) AF: 0.0181 AC: 104 AN: 5754

European-Non Finnish (NFE) AF: 0.00248 AC: 2759 AN: 1111944

Other (OTH) AF: 0.00590 AC: 356 AN: 60376

GnomAD4 genome AF: 0.00344 AC: 524 AN: 152320 Hom.: 8 Cov.: 33 AF XY: 0.00380 AC XY: 283 AN XY: 74472

African (AFR) AF: 0.000746 AC: 31 AN: 41582

American (AMR) AF: 0.00242 AC: 37 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4828

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00298 AC: 203 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.00238

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.15
DANN	Benign	0.75
PhyloP100		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs146015006; hg19: chr17-79073793; COSMIC: COSV58336090; COSMIC: COSV58336090;