7-123661753-T-A

Position:

• chr7-123661753-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207163.3(LMOD2):​c.274-107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 697,618 control chromosomes in the GnomAD database, including 5,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1915 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3765 hom.)
• Consequence: LMOD2 NM_207163.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.603

Genes affected

LMOD2 (HGNC:6648): (leiomodin 2) Enables actin monomer binding activity and tropomyosin binding activity. Involved in actin nucleation; positive regulation of actin filament polymerization; and sarcomere organization. Located in actin filament and sarcomere. Colocalizes with M band. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-123661753-T-A is Benign according to our data. Variant chr7-123661753-T-A is described in ClinVar as [Benign]. Clinvar id is 1279919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMOD2	NM_207163.3	c.274-107T>A		intron_variant		ENST00000458573.3	NP_997046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMOD2	ENST00000458573.3	c.274-107T>A		intron_variant		2	NM_207163.3	ENSP00000411932	P1
LMOD2	ENST00000456238.2	c.274-1286T>A		intron_variant		1		ENSP00000398975

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21725 AN: 152076 Hom.: 1901 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.106 AC: 57555 AN: 545424 Hom.: 3765 AF XY: 0.102 AC XY: 28520 AN XY: 278808

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.0501

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.0527

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0947

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.143 AC: 21781 AN: 152194 Hom.: 1915 Cov.: 32 AF XY: 0.145 AC XY: 10812 AN XY: 74424

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.114

Alfa AF: 0.127 Hom.: 194

Bravo AF: 0.149

Asia WGS AF: 0.147 AC: 510 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.26

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: rs10249257; hg19: chr7-123301807;