22-38087202-G-T

Variant names:

• chr22-38087202-G-T
• rs763422301
• NM_025045.6:c.1181C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025045.6(BAIAP2L2):​c.1181C>A​(p.Thr394Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T394S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041889966).

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.1181C>A	p.Thr394Asn	missense	Exon 11 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.1181C>A	p.Thr394Asn	missense	Exon 11 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1199C>A	p.Thr400Asn	missense	Exon 11 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1181C>A	p.Thr394Asn	missense	Exon 12 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234056 AF XY: 0.00000782

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 AF: 0.00000207 AC: 3 AN: 1452088 Hom.: 0 Cov.: 34 AF XY: 0.00000415 AC XY: 3 AN XY: 722426

African (AFR) AF: 0.00 AC: 0 AN: 32634

American (AMR) AF: 0.00 AC: 0 AN: 42382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39026

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108344

Other (OTH) AF: 0.00 AC: 0 AN: 59944

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.013
DANN	Benign	0.77
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.35	N
PhyloP100		-0.81
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.0050
Sift	Benign	0.51	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.23		Loss of glycosylation at T394 (P = 0.0019)
MVP		0.12
MPC		0.24
ClinPred		0.017	T
GERP RS		-6.9
Varity_R		0.020
gMVP		0.20
Mutation Taster		=95/5	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: rs763422301; hg19: chr22-38483209;