5-137870288-G-GACACACAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006790.3(MYOT):c.-211-121_-211-114dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.049 (215 hom., cov: 0)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 5-137870288-G-GACACACAC is Benign according to our data. Variant chr5-137870288-G-GACACACAC is described in ClinVar as [Benign]. Clinvar id is 1266810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOT	NM_006790.3	c.-211-121_-211-114dup		intron_variant		ENST00000239926.9
PKD2L2-DT	XR_948815.3	n.303-11026_303-11025insGTGTGTGT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOT	ENST00000239926.9	c.-211-121_-211-114dup		intron_variant		1	NM_006790.3	P1
PKD2L2-DT	ENST00000514616.6	n.320-11026_320-11025insGTGTGTGT		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 6205 AN: 126854 Hom.: 216 Cov.: 0

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.0320

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0280

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0358

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

GnomAD4 genome AF: 0.0489 AC: 6211 AN: 126928 Hom.: 215 Cov.: 0 AF XY: 0.0461 AC XY: 2774 AN XY: 60154

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0229

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0360

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35301804; hg19: chr5-137205977;