chr13-97326805-G-A

Variant names:

• chr13-97326805-G-A
• rs10508032
• NM_001382683.1:c.175-7471G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1334 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382683.1. 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.175-7471G>A		intron	N/A	NP_001369612.1
	MBNL2	NM_001382669.1		c.175-7471G>A		intron	N/A	NP_001369598.1
	MBNL2	NM_001382670.1		c.175-7471G>A		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.175-7471G>A		intron	N/A	ENSP00000505596.1
	MBNL2	ENST00000376673.8	TSL:1	c.175-7471G>A		intron	N/A	ENSP00000365861.3
	MBNL2	ENST00000345429.10	TSL:1	c.175-7471G>A		intron	N/A	ENSP00000267287.7

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

African (AFR) AF: 0.00217 AC: 90 AN: 41564

American (AMR) AF: 0.00810 AC: 124 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4828

European-Finnish (FIN) AF: 0.0126 AC: 134 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 817 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.49
PhyloP100		0.24
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: rs10508032; hg19: chr13-97979059;