rs1999088

Variant names:

• chr13-97275350-A-G
• rs1999088
• NM_001382683.1:c.-604-282A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000679496.1(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 ENST00000679496.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3327 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679496.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	NM_001382683.1	MANE Select	c.-604-282A>G		intron	N/A	NP_001369612.1
	MBNL2	NM_001382669.1		c.-604-282A>G		intron	N/A	NP_001369598.1
	MBNL2	NM_001382670.1		c.-604-282A>G		intron	N/A	NP_001369599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	ENST00000679496.1	MANE Select	c.-604-282A>G		intron	N/A	ENSP00000505596.1
	MBNL2	ENST00000376673.8	TSL:1	c.-604-282A>G		intron	N/A	ENSP00000365861.3
	MBNL2	ENST00000345429.10	TSL:1	c.-604-282A>G		intron	N/A	ENSP00000267287.7

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

African (AFR) AF: 0.00363 AC: 151 AN: 41590

American (AMR) AF: 0.00804 AC: 123 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4826

European-Finnish (FIN) AF: 0.0600 AC: 637 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0306 AC: 2085 AN: 68036

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0268 Hom.: 193

Bravo AF: 0.0154

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism

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: rs1999088; hg19: chr13-97927604;