NM_001353788.2:c.261C>T

Variant names:

• chr15-29054145-C-T
• rs112965425
• NM_001353788.2:c.261C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001353788.2(APBA2):​c.261C>T​(p.Asp87Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,614,188 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 0.012 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: APBA2 NM_001353788.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.714
• Publications: 1 publications found

Genes affected

APBA2 (HGNC:579): (amyloid beta precursor protein binding family A member 2) The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2017]

APBA2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-29054145-C-T is Benign according to our data. Variant chr15-29054145-C-T is described in ClinVar as Benign. ClinVar VariationId is 790686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.714 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1762/152304) while in subpopulation AFR AF = 0.0409 (1698/41566). AF 95% confidence interval is 0.0392. There are 40 homozygotes in GnomAd4. There are 820 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1762 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353788.2. 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
	APBA2	NM_001353788.2	MANE Select	c.261C>T	p.Asp87Asp	synonymous	Exon 4 of 15	NP_001340717.1	Q99767-1
	APBA2	NM_001353789.2		c.261C>T	p.Asp87Asp	synonymous	Exon 4 of 15	NP_001340718.1	Q99767-1
	APBA2	NM_001353790.2		c.261C>T	p.Asp87Asp	synonymous	Exon 4 of 15	NP_001340719.1	Q99767-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA2	ENST00000683413.1	MANE Select	c.261C>T	p.Asp87Asp	synonymous	Exon 4 of 15	ENSP00000507394.1	Q99767-1
	APBA2	ENST00000558259.5	TSL:1	c.261C>T	p.Asp87Asp	synonymous	Exon 3 of 14	ENSP00000454171.1	Q99767-1
	APBA2	ENST00000411764.5	TSL:1	c.261C>T	p.Asp87Asp	synonymous	Exon 3 of 13	ENSP00000409312.1	Q99767-2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152186 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00285 AC: 717 AN: 251408 AF XY: 0.00235

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00121 AC: 1766 AN: 1461884 Hom.: 37 Cov.: 32 AF XY: 0.00105 AC XY: 765 AN XY: 727246

African (AFR) AF: 0.0438 AC: 1468 AN: 33480

American (AMR) AF: 0.00157 AC: 70 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1112012

Other (OTH) AF: 0.00250 AC: 151 AN: 60394

GnomAD4 genome AF: 0.0116 AC: 1762 AN: 152304 Hom.: 40 Cov.: 32 AF XY: 0.0110 AC XY: 820 AN XY: 74478

African (AFR) AF: 0.0409 AC: 1698 AN: 41566

American (AMR) AF: 0.00268 AC: 41 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00604 Hom.: 8

Bravo AF: 0.0130

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	APBA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.52
DANN	Benign	0.63
PhyloP100		-0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs112965425; hg19: chr15-29346348;