NM_025045.6:c.1181C>G

Variant names:

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

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>G​(p.Thr394Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,603,912 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BAIAP2L2 NM_025045.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.03489852).

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>G	p.Thr394Ser	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>G	p.Thr394Ser	missense	Exon 11 of 14	ENSP00000371085.3	Q6UXY1-1
	BAIAP2L2	ENST00000871592.1		c.1199C>G	p.Thr400Ser	missense	Exon 11 of 14	ENSP00000541651.1
	BAIAP2L2	ENST00000871591.1		c.1181C>G	p.Thr394Ser	missense	Exon 12 of 15	ENSP00000541650.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151824 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000128 AC: 3 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: 0.000120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 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: 0.0000512 AC: 2 AN: 39026

South Asian (SAS) AF: 0.0000353 AC: 3 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 AF: 0.0000132 AC: 2 AN: 151824 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74128

African (AFR) AF: 0.00 AC: 0 AN: 41282

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000827 AC: 1

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	0.067
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.024
DANN	Benign	0.67
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.23	N
PhyloP100		-0.81
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.0030
Sift	Benign	0.64	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.20		Loss of catalytic residue at T394 (P = 0.079)
MVP		0.14
MPC		0.19
ClinPred		0.0098	T
GERP RS		-6.9
Varity_R		0.021
gMVP		0.21
Mutation Taster		=100/0	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;