2-195926552-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_018897.3(DNAH7):c.3486A>C(p.Ala1162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,591,136 control chromosomes in the GnomAD database, including 314,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (22192 hom., cov: 31)
  • Exomes 𝑓: 0.63 (292325 hom.)
• Consequence: DNAH7 NM_018897.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-195926552-T-G is Benign according to our data. Variant chr2-195926552-T-G is described in ClinVar as [Benign]. Clinvar id is 402753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.184 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3	c.3486A>C	p.Ala1162=	synonymous_variant	22/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11	c.3486A>C	p.Ala1162=	synonymous_variant	22/65	1	NM_018897.3	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75818 AN: 151808 Hom.: 22189 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.501

GnomAD3 exomes AF: 0.597 AC: 137100 AN: 229746 Hom.: 42857 AF XY: 0.605 AC XY: 75753 AN XY: 125300

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.528

Gnomad EAS exome AF: 0.562

Gnomad SAS exome AF: 0.643

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.644

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.631 AC: 908071 AN: 1439210 Hom.: 292325 Cov.: 38 AF XY: 0.632 AC XY: 452432 AN XY: 715978

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.582

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.640

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.499 AC: 75827 AN: 151926 Hom.: 22192 Cov.: 31 AF XY: 0.502 AC XY: 37289 AN XY: 74244

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.499

Alfa AF: 0.616 Hom.: 63791

Bravo AF: 0.472

Asia WGS AF: 0.566 AC: 1965 AN: 3476

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.41
Dann	Benign	0.30

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: rs1489802; hg19: chr2-196791276; COSMIC: COSV56765630;