3-196316347-A-AT

Position:

• chr3-196316347-A-AT

Variant summary

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

The NM_152773.5(DYNLT2B):​c.114-117_114-116insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,046,880 control chromosomes in the GnomAD database, including 2,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (373 hom., cov: 31)
  • Exomes 𝑓: 0.058 (1885 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.446

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]

TM4SF19-DYNLT2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-196316347-A-AT is Benign according to our data. Variant chr3-196316347-A-AT is described in ClinVar as [Benign]. Clinvar id is 1232152.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
DYNLT2B	NM_152773.5	c.114-117_114-116insA		intron_variant		ENST00000325318.10
TM4SF19-DYNLT2B	NR_037950.1	n.862-117_862-116insA		intron_variant, non_coding_transcript_variant
DYNLT2B	NM_001351628.2	c.114-117_114-116insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.114-117_114-116insA		intron_variant		1	NM_152773.5	P1
DYNLT2B	ENST00000426563.5	c.118-117_118-116insA		intron_variant, NMD_transcript_variant		2
DYNLT2B	ENST00000446494.1	c.114-117_114-116insA		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9910 AN: 151910 Hom.: 372 Cov.: 31

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0583 AC: 52152 AN: 894852 Hom.: 1885 AF XY: 0.0599 AC XY: 26369 AN XY: 440454

Gnomad4 AFR exome AF: 0.0683

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0363

Gnomad4 NFE exome AF: 0.0566

Gnomad4 OTH exome AF: 0.0673

GnomAD4 genome AF: 0.0652 AC: 9914 AN: 152028 Hom.: 373 Cov.: 31 AF XY: 0.0656 AC XY: 4878 AN XY: 74316

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0366

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0606

Bravo AF: 0.0651

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

May 19, 2021

- -

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: rs61388787; hg19: chr3-196043218;