rs1999088

Positions:

• chr13-97275350-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001382683.1(MBNL2):​c.-604-282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 152,354 control chromosomes in the GnomAD database, including 75 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 0.022 (75 hom., cov: 32)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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]

LOC101927385 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0218 (3327/152354) while in subpopulation SAS AF= 0.0485 (234/4826). AF 95% confidence interval is 0.0434. There are 75 homozygotes in gnomad4. There are 1731 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.-604-282A>G		intron_variant		ENST00000679496.1	NP_001369612.1
LOC101927385	XR_001749966.2	n.3299+3547T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL2	ENST00000679496.1	c.-604-282A>G		intron_variant			NM_001382683.1	ENSP00000505596

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3330 AN: 152236 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0218 AC: 3327 AN: 152354 Hom.: 75 Cov.: 32 AF XY: 0.0232 AC XY: 1731 AN XY: 74500

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0272 Hom.: 92

Bravo AF: 0.0154

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.80

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: rs1999088; hg19: chr13-97927604;