2-195891811-GAAA-GAA

Position:

• chr2-195891811-GAAA-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018897.3(DNAH7):​c.4897-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51349 hom., cov: 0)
  • Exomes 𝑓: 0.79 (326764 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 2-195891811-GA-G is Benign according to our data. Variant chr2-195891811-GA-G is described in ClinVar as [Benign]. Clinvar id is 402751.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-195891811-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4897-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.4897-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018897.3	ENSP00000311273	P1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 122544 AN: 149490 Hom.: 51322 Cov.: 0

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.837

GnomAD3 exomes AF: 0.810 AC: 124283 AN: 153394 Hom.: 49378 AF XY: 0.811 AC XY: 67219 AN XY: 82892

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.927

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.898

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.793 AC: 853646 AN: 1075898 Hom.: 326764 Cov.: 0 AF XY: 0.795 AC XY: 424464 AN XY: 534044

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.835

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.793

GnomAD4 genome AF: 0.820 AC: 122617 AN: 149600 Hom.: 51349 Cov.: 0 AF XY: 0.825 AC XY: 60232 AN XY: 72996

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.839

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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: rs11292337; hg19: chr2-196756535;