rs2301618

Variant names:

• chr16-20935342-C-G
• rs2301618
• NM_001347886.2:c.11859+6G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-20935342-C-G
• chr16-20935342-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001347886.2(DNAH3):​c.11859+6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH3 NM_001347886.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002620
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

Genes affected

DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH3	NM_001347886.2	c.11859+6G>C		splice_region_variant, intron_variant	Intron 61 of 61	ENST00000698260.1	NP_001334815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH3	ENST00000698260.1	c.11859+6G>C		splice_region_variant, intron_variant	Intron 61 of 61		NM_001347886.2	ENSP00000513632.1
DNAH3	ENST00000261383.3	c.11997+6G>C		splice_region_variant, intron_variant	Intron 61 of 61	1		ENSP00000261383.3
DNAH3	ENST00000685858.1	c.12039+6G>C		splice_region_variant, intron_variant	Intron 61 of 61			ENSP00000508756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.026
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: rs2301618; hg19: chr16-20946664;