rs10508032

Positions:

• chr13-97326805-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001382683.1(MBNL2):​c.175-7471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00876 in 152,318 control chromosomes in the GnomAD database, including 7 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 0.0088 (7 hom., cov: 33)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

Genes affected

MBNL2 (HGNC:16746): (muscleblind like splicing regulator 2) This gene is a member of the muscleblind protein family which was initially described in Drosophila melanogaster. This gene encodes a C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs. Muscleblind proteins bind specifically to expanded dsCUG RNA but not to normal size CUG repeats and may thereby play a role in the pathophysiology of myotonic dystrophy. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00876 (1334/152318) while in subpopulation SAS AF= 0.0315 (152/4828). AF 95% confidence interval is 0.0274. There are 7 homozygotes in gnomad4. There are 662 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.175-7471G>A		intron_variant		ENST00000679496.1	NP_001369612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL2	ENST00000679496.1	c.175-7471G>A		intron_variant			NM_001382683.1	ENSP00000505596

Frequencies

GnomAD3 genomes AF: 0.00877 AC: 1335 AN: 152200 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00430

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

GnomAD4 genome AF: 0.00876 AC: 1334 AN: 152318 Hom.: 7 Cov.: 33 AF XY: 0.00889 AC XY: 662 AN XY: 74480

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00954 Hom.: 1

Bravo AF: 0.00709

Asia WGS AF: 0.00664 AC: 23 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	9.1
DANN	Benign	0.49

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: rs10508032; hg19: chr13-97979059;