rs767911744

Variant names:

• chr7-24663596-G-A
• rs767911744
• NM_001303037.2:c.658G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-24663596-G-A
• chr7-24663596-G-C
• chr7-24663596-G-T

Variant summary

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

The NM_001303037.2(PALS2):​c.658G>A​(p.Val220Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V220L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PALS2 NM_001303037.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• Publications: 3 publications found

Genes affected

PALS2 (HGNC:18167): (protein associated with LIN7 2, MAGUK p55 family member) Members of the peripheral membrane-associated guanylate kinase (MAGUK) family function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. All MAGUKs contain a PDZ-SH3-GUK core and are divided into 4 subfamilies, DLG-like (see DLG1; MIM 601014), ZO1-like (see TJP1; MIM 601009), p55-like (see MPP1; MIM 305360), and LIN2-like (see CASK; MIM 300172), based on their size and the presence of additional domains. MPP6 is a member of the p55-like MAGUK subfamily (Tseng et al., 2001 [PubMed 11311936]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALS2	NM_001303037.2	c.658G>A	p.Val220Met	missense_variant	Exon 6 of 12	ENST00000222644.10	NP_001289966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALS2	ENST00000222644.10	c.658G>A	p.Val220Met	missense_variant	Exon 6 of 12	1	NM_001303037.2	ENSP00000222644.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438194 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 716556

African (AFR) AF: 0.00 AC: 0 AN: 32316

American (AMR) AF: 0.00 AC: 0 AN: 42884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094480

Other (OTH) AF: 0.00 AC: 0 AN: 59514

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;T;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	2.0	M;.;M;.
PhyloP100		4.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.42	T;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.49	P;.;P;.
Vest4		0.53
MutPred		0.57		Gain of catalytic residue at V220 (P = 0.0205);.;Gain of catalytic residue at V220 (P = 0.0205);Gain of catalytic residue at V220 (P = 0.0205);
MVP		0.74
MPC		0.90
ClinPred		0.79	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.51
Mutation Taster		=51/49	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: rs767911744; hg19: chr7-24703215;