rs751151224

Variant names:

• chr3-196316085-T-C
• rs751151224
• NM_152773.5:c.247+13A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-196316085-T-C
• chr3-196316085-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152773.5(DYNLT2B):​c.247+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 0 publications found

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:49190): (TM4SF19-DYNLT2B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring transmembrane 4 L six family member 19 (TM4SF19) and Tctex1 domain containing 2 (TCTEX1D2) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not expected to produce a protein product. [provided by RefSeq, Mar 2011]

ENSG00000272741 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	NM_152773.5	MANE Select	c.247+13A>G		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.247+13A>G		intron	N/A	NP_001338557.1
	TM4SF19-DYNLT2B	NR_037950.1		n.1008A>G		splice_region non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.247+13A>G		intron	N/A	ENSP00000324323.5	Q8WW35
	TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*220A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000405973.1
	TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*220A>G		3_prime_UTR	Exon 6 of 6	ENSP00000405973.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249740 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459574 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726108

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110754

Other (OTH) AF: 0.00 AC: 0 AN: 60272

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		-0.37

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

Other links and lift over

dbSNP: rs751151224; hg19: chr3-196042956;