5-137870126-T-TA

Position:

• chr5-137870126-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006790.3(MYOT):​c.-211-297dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 86,844 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.012 (10 hom., cov: 29)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.449

Genes affected

MYOT (HGNC:12399): (myotilin) This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]

PKD2L2-DT (HGNC:55557): (PKD2L2 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-137870126-T-TA is Benign according to our data. Variant chr5-137870126-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1196566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0122 (1060/86844) while in subpopulation EAS AF= 0.0284 (93/3274). AF 95% confidence interval is 0.0237. There are 10 homozygotes in gnomad4. There are 489 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1060 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOT	NM_006790.3	c.-211-297dup		intron_variant		ENST00000239926.9
PKD2L2-DT	XR_948815.3	n.303-10864_303-10863insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOT	ENST00000239926.9	c.-211-297dup		intron_variant		1	NM_006790.3	P1
PKD2L2-DT	ENST00000514616.6	n.320-10864_320-10863insT		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1059 AN: 86850 Hom.: 10 Cov.: 29

Gnomad AFR AF: 0.00520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00239

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.00810

Gnomad MID AF: 0.0211

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0122 AC: 1060 AN: 86844 Hom.: 10 Cov.: 29 AF XY: 0.0119 AC XY: 489 AN XY: 41264

Gnomad4 AFR AF: 0.00519

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.00239

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.00810

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs566265335; hg19: chr5-137205815;