2-195808809-A-T

Position:

• chr2-195808809-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018897.3(DNAH7):​c.9956T>A​(p.Leu3319His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3319P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22151062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3	c.9956T>A	p.Leu3319His	missense_variant	53/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11	c.9956T>A	p.Leu3319His	missense_variant	53/65	1	NM_018897.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.95	N
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Polyphen		0.11	B
Vest4		0.29
MutPred		0.50		Gain of catalytic residue at L3319 (P = 0.0062);
MVP		0.40
MPC		0.13
ClinPred		0.72	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.55

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: rs13411834; hg19: chr2-196673533;