Genetic Variant BAIAP2L2:p.Pro466Ser (chr22-38086313-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025045.6(BAIAP2L2):c.1396C>T(p.Pro466Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000221 in 1,586,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

BAIAP2L2
NM_025045.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

BAIAP2L2 (HGNC:26203): (BAR/IMD domain containing adaptor protein 2 like 2) The protein encoded by this gene binds phosphoinositides and promotes the formation of planar or curved membrane structures. The encoded protein is found in RAB13-positive vesicles and at intercellular contacts with the plasma membrane. [provided by RefSeq, Dec 2012]

BAIAP2L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14928192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2L2	NM_025045.6 link	c.1396C>T	p.Pro466Ser	missense_variant	Exon 12 of 14	ENST00000381669.8	NP_079321.3	Q6UXY1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP2L2	ENST00000381669.8 link	c.1396C>T	p.Pro466Ser	missense_variant	Exon 12 of 14	1	NM_025045.6	ENSP00000371085.3		Q6UXY1-1

Frequencies

GnomAD3 genomes

AF:

0.00000701

AC:

AN:

142632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000520

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

238224

Hom.:

AF XY:

0.0000461

AC XY:

AN XY:

130218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000948

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1444270

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

717786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

AF:

0.00000701

AC:

AN:

142632

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000520

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1396C>T (p.P466S) alteration is located in exon 12 (coding exon 12) of the BAIAP2L2 gene. This alteration results from a C to T substitution at nucleotide position 1396, causing the proline (P) at amino acid position 466 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

T;.;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.19

T;.;D

Sift4G

Benign

0.090

T;T;D

Polyphen

1.0

D;.;.

Vest4

0.37

MutPred

0.22

Gain of phosphorylation at P466 (P = 0.0023);.;.;

MVP

0.54

MPC

0.77

ClinPred

0.69

GERP RS

4.1

Varity_R

0.091

gMVP

0.31

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