Genetic Variant BAIAP2L2:p.Arg452Cys (chr22-38086355-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025045.6(BAIAP2L2):c.1354C>T(p.Arg452Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 773,186 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

BAIAP2L2
NM_025045.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041573465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2L2	NM_025045.6 link	c.1354C>T	p.Arg452Cys	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.1354C>T	p.Arg452Cys	missense_variant	Exon 12 of 14	1	NM_025045.6	ENSP00000371085.3		Q6UXY1-1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

89948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000833

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000233

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000351

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

215356

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

117506

show subpopulations

Gnomad AFR exome

AF:

0.000831

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000585

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

130

AN:

683124

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

337348

show subpopulations

Gnomad4 AFR exome

AF:

0.000639

Gnomad4 AMR exome

AF:

0.0000509

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000466

AC:

AN:

90062

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

AN XY:

44340

show subpopulations

Gnomad4 AFR

AF:

0.000830

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000233

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000142

Gnomad4 NFE

AF:

0.000351

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000405

AC:

ExAC

AF:

0.000240

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1354C>T (p.R452C) 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 1354, causing the arginine (R) at amino acid position 452 to be replaced by a cysteine (C). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.093

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.19

Sift

Benign

0.043

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

1.0

D;.

Vest4

0.28

MVP

0.56

MPC

0.29

ClinPred

0.13

GERP RS

4.4

Varity_R

0.087

gMVP

0.20

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