NM_025045.6:c.1361G>A

Variant names:

• chr22-38086348-C-T
• rs113792005
• NM_025045.6:c.1361G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_025045.6(BAIAP2L2):​c.1361G>A​(p.Arg454His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 774,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R454C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000056 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.947
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.158).

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.1361G>A	p.Arg454His	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.1361G>A	p.Arg454His	missense	Exon 12 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1379G>A	p.Arg460His	missense	Exon 12 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1361G>A	p.Arg454His	missense	Exon 13 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes AF: 0.0000560 AC: 5 AN: 89266 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00182

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000183 AC: 4 AN: 218116 AF XY: 0.0000252

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: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000204 AC: 14 AN: 684656 Hom.: 0 Cov.: 0 AF XY: 0.0000266 AC XY: 9 AN XY: 338222

African (AFR) AF: 0.00 AC: 0 AN: 28236

American (AMR) AF: 0.00 AC: 0 AN: 19670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9956

East Asian (EAS) AF: 0.00 AC: 0 AN: 30496

South Asian (SAS) AF: 0.000212 AC: 8 AN: 37752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2608

European-Non Finnish (NFE) AF: 0.00000607 AC: 3 AN: 494300

Other (OTH) AF: 0.000104 AC: 3 AN: 28840

GnomAD4 genome AF: 0.0000559 AC: 5 AN: 89380 Hom.: 0 Cov.: 25 AF XY: 0.000114 AC XY: 5 AN XY: 43976

African (AFR) AF: 0.0000287 AC: 1 AN: 34830

American (AMR) AF: 0.00 AC: 0 AN: 7054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1496

East Asian (EAS) AF: 0.00 AC: 0 AN: 4276

South Asian (SAS) AF: 0.00182 AC: 4 AN: 2196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6988

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 30998

Other (OTH) AF: 0.00 AC: 0 AN: 1078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000301 AC: 2

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	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.0094	T
PhyloP100		0.95
ClinPred		0.090	T
GERP RS		2.3
Varity_R		0.066
Mutation Taster		=94/6	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: rs113792005; hg19: chr22-38482355;