22-38086349-G-C

Variant names:

• chr22-38086349-G-C
• rs749648034
• NM_025045.6:c.1360C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025045.6(BAIAP2L2):​c.1360C>G​(p.Arg454Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 684,766 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 25)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.144).

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.1360C>G	p.Arg454Gly	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.1360C>G	p.Arg454Gly	missense	Exon 12 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1378C>G	p.Arg460Gly	missense	Exon 12 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1360C>G	p.Arg454Gly	missense	Exon 13 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000146 AC: 1 AN: 684766 Hom.: 0 Cov.: 0 AF XY: 0.00000296 AC XY: 1 AN XY: 338346

African (AFR) AF: 0.00 AC: 0 AN: 28266

American (AMR) AF: 0.00 AC: 0 AN: 19754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9994

East Asian (EAS) AF: 0.00 AC: 0 AN: 30506

South Asian (SAS) AF: 0.00 AC: 0 AN: 37806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2624

European-Non Finnish (NFE) AF: 0.00000202 AC: 1 AN: 494044

Other (OTH) AF: 0.00 AC: 0 AN: 28874

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.098	N
M_CAP	Benign	0.0096	T
PhyloP100		1.2
ClinPred		0.29	T
GERP RS		1.9
Varity_R		0.079
Mutation Taster		=93/7	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: rs749648034; hg19: chr22-38482356;