2-195740780-C-T

Variant names:

• chr2-195740780-C-T
• NM_018897.3:c.11854G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018897.3(DNAH7):​c.11854G>A​(p.Asp3952Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,389,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

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]

LOC107985972 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.11854G>A	p.Asp3952Asn	missense_variant	Exon 64 of 65	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.11854G>A	p.Asp3952Asn	missense_variant	Exon 64 of 65	1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000409063.5	c.1303G>A	p.Asp435Asn	missense_variant	Exon 9 of 10	1		ENSP00000386912.1
DNAH7	ENST00000438565.1	c.156G>A	p.Met52Ile	missense_variant	Exon 2 of 3	3		ENSP00000409732.1
DNAH7	ENST00000484183.1	n.352G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389360 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 689244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000259

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11854G>A (p.D3952N) alteration is located in exon 64 (coding exon 64) of the DNAH7 gene. This alteration results from a G to A substitution at nucleotide position 11854, causing the aspartic acid (D) at amino acid position 3952 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.23
Sift	Benign	0.044	D;D
Sift4G	Benign	0.080	T;.
Polyphen		0.76	.;P
Vest4		0.74
MutPred		0.79		.;Gain of MoRF binding (P = 0.0513);
MVP		0.37
MPC		0.18
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.50
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-196605504;