7-24652933-G-C

Variant names:

• chr7-24652933-G-C
• rs2721800
• NM_001303037.2:c.651+2221G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303037.2(PALS2):​c.651+2221G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,148 control chromosomes in the GnomAD database, including 1,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (1925 hom., cov: 32)
• Consequence: PALS2 NM_001303037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303037.2. 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
	PALS2	NM_001303037.2	MANE Select	c.651+2221G>C		intron	N/A	NP_001289966.1	Q9NZW5
	PALS2	NM_016447.4		c.651+2221G>C		intron	N/A	NP_057531.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALS2	ENST00000222644.10	TSL:1 MANE Select	c.651+2221G>C		intron	N/A	ENSP00000222644.4	Q9NZW5
	PALS2	ENST00000396475.6	TSL:1	c.651+2221G>C		intron	N/A	ENSP00000379737.2	Q9NZW5
	PALS2	ENST00000896217.1		c.651+2221G>C		intron	N/A	ENSP00000566276.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23929 AN: 152030 Hom.: 1923 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23944 AN: 152148 Hom.: 1925 Cov.: 32 AF XY: 0.153 AC XY: 11361 AN XY: 74374

African (AFR) AF: 0.156 AC: 6464 AN: 41500

American (AMR) AF: 0.164 AC: 2499 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 285 AN: 3468

East Asian (EAS) AF: 0.0582 AC: 302 AN: 5188

South Asian (SAS) AF: 0.133 AC: 644 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1496 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11818 AN: 67992

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.145 Hom.: 990

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

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: rs2721800; hg19: chr7-24692552;