2-196001709-A-G

Variant names:

• chr2-196001709-A-G
• NM_018897.3:c.1139T>C

Variant summary

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

The NM_018897.3(DNAH7):​c.1139T>C​(p.Met380Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M380R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 65	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 65	1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000410072.5	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 13	2		ENSP00000386260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440414 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715016

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: 9.07e-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	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.011	.;D
Polyphen		0.35	B;.
Vest4		0.66
MutPred		0.66		Loss of stability (P = 0.0441);Loss of stability (P = 0.0441);
MVP		0.26
MPC		0.037
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-196866433; COSMIC: COSV100413845;