chr2-69924339-A-G

Position:

• chr2-69924339-A-G

Variant summary

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

The NM_002357.4(MXD1):​c.203+2574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,082 control chromosomes in the GnomAD database, including 23,358 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 0.53 (23358 hom., cov: 33)
• Consequence: MXD1 NM_002357.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

Genes affected

MXD1 (HGNC:6761): (MAX dimerization protein 1) This gene encodes a member of the MYC/MAX/MAD network of basic helix-loop-helix leucine zipper transcription factors. The MYC/MAX/MAD transcription factors mediate cellular proliferation, differentiation and apoptosis. The encoded protein antagonizes MYC-mediated transcriptional activation of target genes by competing for the binding partner MAX and recruiting repressor complexes containing histone deacetylases. Mutations in this gene may play a role in acute leukemia, and the encoded protein is a potential tumor suppressor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXD1	NM_002357.4	c.203+2574A>G		intron_variant		ENST00000264444.7	NP_002348.1
MXD1	NM_001202513.2	c.203+2574A>G		intron_variant			NP_001189442.1
MXD1	NM_001202514.2	c.173+8119A>G		intron_variant			NP_001189443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXD1	ENST00000264444.7	c.203+2574A>G		intron_variant		1	NM_002357.4	ENSP00000264444	P1
MXD1	ENST00000540449.5	c.173+8119A>G		intron_variant		1		ENSP00000443935
MXD1	ENST00000435990.5	c.107+2574A>G		intron_variant		3		ENSP00000410672
MXD1	ENST00000409442.2	c.77+8119A>G		intron_variant, NMD_transcript_variant		2		ENSP00000386523

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80768 AN: 151964 Hom.: 23320 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.532 AC: 80851 AN: 152082 Hom.: 23358 Cov.: 33 AF XY: 0.532 AC XY: 39551 AN XY: 74334

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.467

Alfa AF: 0.468 Hom.: 5893

Bravo AF: 0.535

Asia WGS AF: 0.549 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs10205487; hg19: chr2-70151471;