NM_001370.2:c.7649T>G

Variant names:

• chr2-84697699-T-G
• NM_001370.2:c.7649T>G

Variant summary

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

The NM_001370.2(DNAH6):​c.7649T>G​(p.Val2550Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 7.1e-7 (0 hom.)
• Consequence: DNAH6 NM_001370.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) 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. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 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 (MetaRNN=0.029125273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.7649T>G	p.Val2550Gly	missense_variant	Exon 47 of 77	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.7649T>G	p.Val2550Gly	missense_variant	Exon 47 of 77	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000602588.1	n.1730T>G		non_coding_transcript_exon_variant	Exon 11 of 11	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399548 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690282

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.30
DANN	Benign	0.89
DEOGEN2	Benign	0.0083	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T;.
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.27	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.050
Sift	Benign	0.28	T;T
Polyphen		0.019	B;B
Vest4		0.21
MutPred		0.38		Loss of stability (P = 0.0106);Loss of stability (P = 0.0106);
MVP		0.076
MPC		0.13
ClinPred		0.14	T
GERP RS		-11
Varity_R		0.28
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-84924823;