3-196296136-C-T

Position:

• chr3-196296136-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000325318.10(DYNLT2B):​c.318-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,323,530 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (380 hom., cov: 32)
  • Exomes 𝑓: 0.065 (2989 hom.)
• Consequence: DYNLT2B ENST00000325318.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37

Genes affected

DYNLT2B (HGNC:28482): (dynein light chain Tctex-type 2B) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains. This gene encodes a subunit of the human cytoplasmic dynein-2 complex. Mutations in this gene are associated with short-rib thoracic dysplasia 17 with or without polydactyly. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-196296136-C-T is Benign according to our data. Variant chr3-196296136-C-T is described in ClinVar as [Benign]. Clinvar id is 1262426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLT2B	NM_152773.5	c.318-67G>A		intron_variant		ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2	c.318-67G>A		intron_variant			NP_001338557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.318-67G>A		intron_variant		1	NM_152773.5	ENSP00000324323	P1
DYNLT2B	ENST00000465757.5	n.171G>A		non_coding_transcript_exon_variant	1/2	2
DYNLT2B	ENST00000426563.5	c.*184-67G>A		intron_variant, NMD_transcript_variant		2		ENSP00000415835
DYNLT2B	ENST00000446494.1	c.*37-67G>A		intron_variant, NMD_transcript_variant		3		ENSP00000410605

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9956 AN: 152134 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.0653 AC: 76540 AN: 1171278 Hom.: 2989 Cov.: 16 AF XY: 0.0682 AC XY: 40655 AN XY: 596286

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.0336

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0170

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.0630

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.0654 AC: 9960 AN: 152252 Hom.: 380 Cov.: 32 AF XY: 0.0659 AC XY: 4902 AN XY: 74434

Gnomad4 AFR AF: 0.0760

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0167

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0678 Hom.: 36

Bravo AF: 0.0652

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.024
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73212151; hg19: chr3-196023007;