22-38086376-C-T

Variant names:

• chr22-38086376-C-T
• rs541462698
• NM_025045.6:c.1333G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025045.6(BAIAP2L2):​c.1333G>A​(p.Glu445Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000333 in 90,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04623565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025045.6. 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
	BAIAP2L2	NM_025045.6	MANE Select	c.1333G>A	p.Glu445Lys	missense	Exon 12 of 14	NP_079321.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAIAP2L2	ENST00000381669.8	TSL:1 MANE Select	c.1333G>A	p.Glu445Lys	missense	Exon 12 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1351G>A	p.Glu451Lys	missense	Exon 12 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1333G>A	p.Glu445Lys	missense	Exon 13 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes AF: 0.0000333 AC: 3 AN: 90030 Hom.: 0 Cov.: 25

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: 0.00133

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000441 AC: 9 AN: 203994 AF XY: 0.0000720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000429 AC: 29 AN: 675238 Hom.: 0 Cov.: 0 AF XY: 0.0000721 AC XY: 24 AN XY: 332832

African (AFR) AF: 0.00 AC: 0 AN: 27874

American (AMR) AF: 0.00 AC: 0 AN: 18980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9714

East Asian (EAS) AF: 0.00 AC: 0 AN: 29754

South Asian (SAS) AF: 0.000764 AC: 28 AN: 36644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 488952

Other (OTH) AF: 0.0000352 AC: 1 AN: 28434

GnomAD4 genome AF: 0.0000333 AC: 3 AN: 90142 Hom.: 0 Cov.: 25 AF XY: 0.0000676 AC XY: 3 AN XY: 44380

African (AFR) AF: 0.00 AC: 0 AN: 34924

American (AMR) AF: 0.00 AC: 0 AN: 7138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1516

East Asian (EAS) AF: 0.00 AC: 0 AN: 4286

South Asian (SAS) AF: 0.00133 AC: 3 AN: 2248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31408

Other (OTH) AF: 0.00 AC: 0 AN: 1086

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000106 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.081
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.045	D
Polyphen		0.18	B
Vest4		0.27
MVP		0.52
MPC		0.27
ClinPred		0.17	T
GERP RS		4.4
Varity_R		0.22
gMVP		0.27
Mutation Taster		=96/4	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: rs541462698; hg19: chr22-38482383;