2-196047343-A-G

Variant names:

• chr2-196047343-A-G
• rs4850381
• NM_018897.3:c.398+9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018897.3(DNAH7):​c.398+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,559,550 control chromosomes in the GnomAD database, including 411,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40771 hom., cov: 31)
  • Exomes 𝑓: 0.72 (371203 hom.)
• Consequence: DNAH7 NM_018897.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.768
• Publications: 11 publications found

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]

DNAH7 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 50

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-196047343-A-G is Benign according to our data. Variant chr2-196047343-A-G is described in ClinVar as Benign. ClinVar VariationId is 402757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.398+9T>C		intron	N/A	NP_061720.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.398+9T>C		intron	N/A	ENSP00000311273.6
	DNAH7	ENST00000410072.5	TSL:2	c.398+9T>C		intron	N/A	ENSP00000386260.1
	DNAH7	ENST00000427816.1	TSL:4	c.323+9T>C		intron	N/A	ENSP00000407444.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111014 AN: 151952 Hom.: 40714 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.711

GnomAD2 exomes AF: 0.734 AC: 169040 AN: 230366 AF XY: 0.727

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.903

Gnomad FIN exome AF: 0.735

Gnomad NFE exome AF: 0.713

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.724 AC: 1019497 AN: 1407480 Hom.: 371203 Cov.: 35 AF XY: 0.721 AC XY: 503865 AN XY: 698366

African (AFR) AF: 0.745 AC: 23581 AN: 31640

American (AMR) AF: 0.785 AC: 31901 AN: 40638

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 15339 AN: 24618

East Asian (EAS) AF: 0.919 AC: 35081 AN: 38156

South Asian (SAS) AF: 0.693 AC: 52180 AN: 75260

European-Finnish (FIN) AF: 0.737 AC: 38081 AN: 51664

Middle Eastern (MID) AF: 0.554 AC: 3078 AN: 5560

European-Non Finnish (NFE) AF: 0.720 AC: 778674 AN: 1082116

Other (OTH) AF: 0.719 AC: 41582 AN: 57828

GnomAD4 genome AF: 0.731 AC: 111130 AN: 152070 Hom.: 40771 Cov.: 31 AF XY: 0.732 AC XY: 54399 AN XY: 74336

African (AFR) AF: 0.745 AC: 30894 AN: 41464

American (AMR) AF: 0.741 AC: 11322 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3468

East Asian (EAS) AF: 0.904 AC: 4690 AN: 5188

South Asian (SAS) AF: 0.703 AC: 3392 AN: 4822

European-Finnish (FIN) AF: 0.730 AC: 7723 AN: 10574

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48644 AN: 67974

Other (OTH) AF: 0.712 AC: 1499 AN: 2104

Alfa AF: 0.717 Hom.: 142957

Bravo AF: 0.733

Asia WGS AF: 0.792 AC: 2755 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.35
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4850381; hg19: chr2-196912067;