rs2336030

chr1-11676543-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006341.4(MAD2L2):c.332+305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,192 control chromosomes in the GnomAD database, including 6,380 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 0.26 (6380 hom., cov: 33)
• Consequence: MAD2L2 NM_006341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

MAD2L2 (HGNC:6764): (mitotic arrest deficient 2 like 2) The protein encoded by this gene is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. The encoded protein, which is similar to MAD2L1, is capable of interacting with ADAM9, ADAM15, REV1, and REV3 proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD2L2	NM_006341.4	c.332+305G>A		intron_variant		ENST00000376692.9
MAD2L2	NM_001127325.2	c.332+305G>A		intron_variant
MAD2L2	XM_047430782.1	c.332+305G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD2L2	ENST00000376692.9	c.332+305G>A		intron_variant		1	NM_006341.4	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39415 AN: 152074 Hom.: 6391 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.259 AC: 39384 AN: 152192 Hom.: 6380 Cov.: 33 AF XY: 0.258 AC XY: 19210 AN XY: 74416

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.292

Alfa AF: 0.324 Hom.: 13538

Bravo AF: 0.253

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.7
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2336030; hg19: chr1-11736600; COSMIC: COSV52418087; COSMIC: COSV52418087;