5-137870288-GACACAC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006790.3(MYOT):c.-211-119_-211-114del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (115 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.475

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 5-137870288-GACACAC-G is Benign according to our data. Variant chr5-137870288-GACACAC-G is described in ClinVar as [Benign]. Clinvar id is 1295552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 3079 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOT	NM_006790.3	c.-211-119_-211-114del		intron_variant		ENST00000239926.9
PKD2L2-DT	XR_948815.3	n.303-11031_303-11026del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOT	ENST00000239926.9	c.-211-119_-211-114del		intron_variant		1	NM_006790.3	P1
PKD2L2-DT	ENST00000514616.6	n.320-11031_320-11026del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3079 AN: 127002 Hom.: 115 Cov.: 0

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000345

Gnomad OTH AF: 0.0176

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0243 AC: 3083 AN: 127074 Hom.: 115 Cov.: 0 AF XY: 0.0241 AC XY: 1451 AN XY: 60224

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000345

Gnomad4 OTH AF: 0.0174

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

Nov 07, 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;