Variant chr22-38086324-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025045.6(BAIAP2L2):c.1385G>A(p.Arg462His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,603,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

BAIAP2L2
NM_025045.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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:

BAIAP2L2 (HGNC:):

BAIAP2L2 links:

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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=0.06646803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAIAP2L2	NM_025045.6 linkuse as main transcript	c.1385G>A	p.Arg462His	missense_variant	12/14	ENST00000381669.8	NP_079321.3	Q6UXY1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAIAP2L2	ENST00000381669.8 linkuse as main transcript	c.1385G>A	p.Arg462His	missense_variant	12/14	1	NM_025045.6	ENSP00000371085.3		Q6UXY1-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000162

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000734

AC:

AN:

231548

Hom.:

AF XY:

0.0000554

AC XY:

AN XY:

126362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000869

Gnomad OTH exome

AF:

0.000361

GnomAD4 exome

AF:

0.000214

AC:

311

AN:

1451116

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

153

AN XY:

720848

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000260

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000138

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000110

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000581

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.1385G>A (p.R462H) alteration is located in exon 12 (coding exon 12) of the BAIAP2L2 gene. This alteration results from a G to A substitution at nucleotide position 1385, causing the arginine (R) at amino acid position 462 to be replaced by a histidine (H). 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

0.077

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.19

Sift

Benign

0.52

T;.;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.95

P;.;.

Vest4

0.20

MutPred

0.29

Loss of methylation at R462 (P = 0.009);.;.;

MVP

0.39

MPC

0.26

ClinPred

0.051

GERP RS

1.5

Varity_R

0.033

gMVP

0.17

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