rs738144

chr22-38782370-G-Achr22-38782370-G-Cchr22-38782370-G-T

Variant summary

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

The NM_005740.3(DNAL4):c.69+293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,228 control chromosomes in the GnomAD database, including 53,502 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 0.84 (53502 hom., cov: 35)
• Consequence: DNAL4 NM_005740.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

DNAL4 (HGNC:2955): (dynein axonemal light chain 4) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. [provided by RefSeq, Dec 2014]

SUN2 (HGNC:14210): (Sad1 and UNC84 domain containing 2) SUN1 (MIM 607723) and SUN2 are inner nuclear membrane (INM) proteins that play a major role in nuclear-cytoplasmic connection by formation of a 'bridge' across the nuclear envelope, known as the LINC complex, via interaction with the conserved luminal KASH domain of nesprins (e.g., SYNE1; MIM 608441) located in the outer nuclear membrane (ONM). The LINC complex provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity (summary by Haque et al., 2010 [PubMed 19933576]).[supplied by OMIM, Nov 2010]

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 (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL4	NM_005740.3	c.69+293C>T		intron_variant		ENST00000216068.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL4	ENST00000216068.9	c.69+293C>T		intron_variant		1	NM_005740.3	P1
DNAL4	ENST00000406199.3	c.69+293C>T		intron_variant		2
SUN2	ENST00000406622.5	c.-138+11698C>T		intron_variant		2		P2
DNAL4	ENST00000486019.1	n.82-2757C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127415 AN: 152110 Hom.: 53447 Cov.: 35

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.838 AC: 127529 AN: 152228 Hom.: 53502 Cov.: 35 AF XY: 0.837 AC XY: 62280 AN XY: 74430

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.831

Alfa AF: 0.831 Hom.: 11479

Bravo AF: 0.844

Asia WGS AF: 0.878 AC: 3054 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	0.082
Dann	Benign	0.68

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: rs738144; hg19: chr22-39178375;