22-38086418-C-A

Variant names:

• chr22-38086418-C-A
• rs377442253
• NM_025045.6:c.1291G>T

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.1291G>T​(p.Asp431Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,828 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. 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. D431N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• 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 (MetaRNN=0.20412514).

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.1291G>T	p.Asp431Tyr	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.1291G>T	p.Asp431Tyr	missense	Exon 12 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1309G>T	p.Asp437Tyr	missense	Exon 12 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1291G>T	p.Asp431Tyr	missense	Exon 13 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 677154

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31402

American (AMR) AF: 0.00 AC: 0 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.0000443 AC: 1 AN: 22596

East Asian (EAS) AF: 0.00 AC: 0 AN: 36170

South Asian (SAS) AF: 0.00 AC: 0 AN: 75186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066156

Other (OTH) AF: 0.00 AC: 0 AN: 56678

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.19
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.090
Sift	Benign	0.063	T
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.21		Gain of phosphorylation at D431 (P = 0.0153)
MVP		0.59
MPC		0.85
ClinPred		0.98	D
GERP RS		-0.15
Varity_R		0.19
gMVP		0.46
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377442253; hg19: chr22-38482425;