rs2274987

Positions:

• chr1-66755704-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152665.3(DYNLT5):​c.119+927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,088 control chromosomes in the GnomAD database, including 5,696 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 0.27 (5696 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DYNLT5 NM_152665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

Genes affected

DYNLT5 (HGNC:26882): (dynein light chain Tctex-type family member 5) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNLT5	NM_152665.3	c.119+927T>C		intron_variant		ENST00000282670.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNLT5	ENST00000282670.7	c.119+927T>C		intron_variant		1	NM_152665.3	P1
DYNLT5	ENST00000528352.1	c.119+927T>C		intron_variant, NMD_transcript_variant		1
DYNLT5	ENST00000491611.1	n.200T>C		non_coding_transcript_exon_variant	3/5	2
DYNLT5	ENST00000525663.5	n.248+927T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41190 AN: 151970 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.271 AC: 41196 AN: 152088 Hom.: 5696 Cov.: 32 AF XY: 0.269 AC XY: 20006 AN XY: 74372

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.283

Alfa AF: 0.284 Hom.: 10366

Bravo AF: 0.274

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.66

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: rs2274987; hg19: chr1-67221387;