1-50419101-CCGGCGG-C

Position:

• chr1-50419101-CCGGCGG-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_032110.3(DMRTA2):​c.1187_1192delCCGCCG​(p.Ala396_Ala397del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.172 in 1,140,380 control chromosomes in the GnomAD database, including 18,629 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A396A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.14 (1632 hom., cov: 29)
  • Exomes 𝑓: 0.18 (16997 hom.)
• Consequence: DMRTA2 NM_032110.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.32

Genes affected

DMRTA2 (HGNC:13908): (DMRT like family A2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to act upstream of or within nervous system development and skeletal muscle cell differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_032110.3
• BP6: Variant 1-50419101-CCGGCGG-C is Benign according to our data. Variant chr1-50419101-CCGGCGG-C is described in ClinVar as [Benign]. Clinvar id is 1337074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA2	NM_032110.3	c.1187_1192delCCGCCG	p.Ala396_Ala397del	disruptive_inframe_deletion	3/3	ENST00000404795.4	NP_115486.1
DMRTA2	XM_011541937.3	c.1187_1192delCCGCCG	p.Ala396_Ala397del	disruptive_inframe_deletion	2/2		XP_011540239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTA2	ENST00000404795.4	c.1187_1192delCCGCCG	p.Ala396_Ala397del	disruptive_inframe_deletion	3/3	5	NM_032110.3	ENSP00000383909.3
DMRTA2	ENST00000418121.5	c.1187_1192delCCGCCG	p.Ala396_Ala397del	disruptive_inframe_deletion	2/2	1		ENSP00000399370.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 19787 AN: 141274 Hom.: 1626 Cov.: 29

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.243 AC: 81 AN: 334 Hom.: 10 AF XY: 0.263 AC XY: 51 AN XY: 194

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 1.00

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.177 AC: 176914 AN: 999030 Hom.: 16997 AF XY: 0.178 AC XY: 84465 AN XY: 475572

Gnomad4 AFR exome AF: 0.0408

Gnomad4 AMR exome AF: 0.0884

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.140 AC: 19793 AN: 141350 Hom.: 1632 Cov.: 29 AF XY: 0.140 AC XY: 9634 AN XY: 68744

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.152

Bravo AF: 0.128

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

Genetic Services Laboratory, University of Chicago

Oct 17, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4027495; hg19: chr1-50884773;