22-38086418-C-G

Variant names:

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

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>C​(p.Asp431His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.1785368).

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>C	p.Asp431His	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>C	p.Asp431His	missense	Exon 12 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1309G>C	p.Asp437His	missense	Exon 12 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1291G>C	p.Asp431His	missense	Exon 13 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1377838 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 677158

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

American (AMR) AF: 0.00 AC: 0 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22596

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 75188

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: 0.00 AC: 0 AN: 1066162

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.19
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.085
Sift	Benign	0.13	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.21		Loss of stability (P = 0.1297)
MVP		0.53
MPC		0.79
ClinPred		0.94	D
GERP RS		-0.15
Varity_R		0.10
gMVP		0.41
Mutation Taster		=88/12	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: rs377442253; hg19: chr22-38482425;